Molecules

14 pages, 1947 KiB

Open AccessArticle

Design and Synthesis of Some New Furan-Based Derivatives and Evaluation of In Vitro Cytotoxic Activity

by Syed Nasir Abbas Bukhari, Hasan Ejaz, Mervat A. Elsherif, Kashaf Junaid, Islam Zaki and Reham E. Masoud

Molecules 2022, 27(8), 2606; https://doi.org/10.3390/molecules27082606 - 18 Apr 2022

Cited by 7 | Viewed by 2806

Abstract

New furan-based derivatives have been, designed, synthesized, and evaluated for their cytotoxic and tubulin polymerization inhibitory activities. DNA flow cytometric study of pyridine carbohydrazide 4 and N-phenyl triazinone 7 demonstrated G₂/M phase cell cycle disruptions. Accumulation of cells in the [...] Read more.

New furan-based derivatives have been, designed, synthesized, and evaluated for their cytotoxic and tubulin polymerization inhibitory activities. DNA flow cytometric study of pyridine carbohydrazide 4 and N-phenyl triazinone 7 demonstrated G₂/M phase cell cycle disruptions. Accumulation of cells in the pre-G1 phase and positive annexin V/PI staining, which may be caused by degeneration or fragmentation of the genetic components, suggested that cell death occurs via an apoptotic cascade. Furthermore, compounds 4 and 7 had a strong pro-apoptotic impact through inducing the intrinsic mitochondrial mechanism of apoptosis. This mechanistic route was verified by an ELISA experiment that indicated a considerable rise in the levels of p53 and Bax and a drop in the level of Bcl-2 when compared with the control. Full article

(This article belongs to the Section Bioorganic Chemistry)

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15 pages, 3392 KiB

Open AccessArticle

Excretion, Metabolism, and Tissue Distribution of Gelsemium elegans (Gardn. & Champ.) Benth in Pigs

by Xiao Ma, Zi-Yuan Wang, Meng-Ting Zuo, Kun Yang, Zhi-Liang Sun, Yong Wu and Zhao-Ying Liu

Molecules 2022, 27(8), 2605; https://doi.org/10.3390/molecules27082605 - 18 Apr 2022

Cited by 8 | Viewed by 2308

Abstract

Gelsemium elegans (Gardn. & Champ.) Benth is a toxic flowering plant in the family Loganiaceae used to treat skin diseases, neuralgia and acute pain. The high toxicity of G. elegans restricts its development and clinical applications, but in veterinary applications, G. [...] Read more.

Gelsemium elegans (Gardn. & Champ.) Benth is a toxic flowering plant in the family Loganiaceae used to treat skin diseases, neuralgia and acute pain. The high toxicity of G. elegans restricts its development and clinical applications, but in veterinary applications, G. elegans has been fed to pigs as a feed additive without poisoning. However, until now, the in vivo processes of the multiple components of G. elegans have not been studied. This study investigates the excretion, metabolism and tissue distribution of the multiple components of G. elegans after feeding it to pigs in medicated feed. Pigs were fed 2% G. elegans powder in feed for 45 days. The plasma, urine, bile, feces and tissues (heart, liver, lung, spleen, brain, spinal cord, adrenal gland, testis, thigh muscle, abdominal muscle and back muscle) were collected 6 h after the last feeding and analyzed using high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Five natural products in plasma, twelve natural products and five metabolites in urine, and three natural products in feces were characterized, suggesting that multiple components from G. elegans were excreted in the urine. However, ten natural products and four metabolites were detected in bile samples, which suggested that G. elegans is involved in enterohepatic circulation in pigs. A total of seven of these metabolites were characterized, and four metabolites were glucuronidated metabolites. Ten natural products and six metabolites were detected in the tissues, which indicates that G. elegans is widely distributed in tissues and can cross the blood-brain barrier. Among the characterized compounds, a highly toxic gelsedine-type alkaloid from G. elegans was the main compound detected in all biological samples. This is the first study of the excretion, metabolism and tissue distribution of multiple components from G. elegans in pigs. These data can provide an important reference to explain the efficacy and toxicity of G. elegans. Additionally, the results of the tissue distribution of G. elegans are of great value for further residue depletion studies and safety evaluations of products of animals fed G. elegans. Full article

(This article belongs to the Special Issue Exploration on Pharmacokinetics and Pharmacodynamics of Natural Molecules: Current Status and Future Perspectives)

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14 pages, 1484 KiB

Open AccessArticle

Mechanochemical Dimerization of Aldoximes to Furoxans

by Run-Kai Fang, Kuan Chen, Chuang Niu and Guan-Wu Wang

Molecules 2022, 27(8), 2604; https://doi.org/10.3390/molecules27082604 - 18 Apr 2022

Cited by 2 | Viewed by 2659

Abstract

Solvent-free mechanical milling is a new, environmentally friendly and cost-effective technology that is now widely used in the field of organic synthesis. The mechanochemical solvent-free synthesis of furoxans from aldoximes was achieved through dimerization of the in situ generated nitrile oxides in the [...] Read more.

Solvent-free mechanical milling is a new, environmentally friendly and cost-effective technology that is now widely used in the field of organic synthesis. The mechanochemical solvent-free synthesis of furoxans from aldoximes was achieved through dimerization of the in situ generated nitrile oxides in the presence of sodium chloride, Oxone and a base. A variety of furoxans was obtained with up to a 92% yield. The present protocol has the advantages of high reaction efficiency and mild reaction conditions. Full article

(This article belongs to the Special Issue Mechanochemical Synthesis of Organic Compounds)

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12 pages, 2772 KiB

Open AccessArticle

Total Synthesis of Eliglustat via Diastereoselective Amination of Chiral para-Methoxycinnamyl Benzyl Ether

by Younggyu Kong, Pulla Reddy Boggu, Gi Min Park, Yeon Su Kim, Seong Hwan An, In Su Kim and Young Hoon Jung

Molecules 2022, 27(8), 2603; https://doi.org/10.3390/molecules27082603 - 18 Apr 2022

Cited by 2 | Viewed by 3118

Abstract

Eliglustat (Cerdelga^®, Genzyme Corp. Cambridge, MA, USA) is an approved drug for a non-neurological type of Gaucher disease. Herein, we describe the total synthesis of eliglustat 1 starting from readily available 1,4-benzodioxan-6-carbaldehyde via Sharpless asymmetric dihydroxylation and diastereoselective amination of chiral [...] Read more.

Eliglustat (Cerdelga^®, Genzyme Corp. Cambridge, MA, USA) is an approved drug for a non-neurological type of Gaucher disease. Herein, we describe the total synthesis of eliglustat 1 starting from readily available 1,4-benzodioxan-6-carbaldehyde via Sharpless asymmetric dihydroxylation and diastereoselective amination of chiral para-methoxycinnamyl benzyl ethers using chlorosulfonyl isocyanate as the key steps. Notably, the reaction between syn-1,2-dibenzyl ether 6 and chlorosulfonyl isocyanate in the mixture of toluene and hexane (10:1) afforded syn-1,2-amino alcohol 5 at a 62% yield with a diastereoselectivity > 20:1. This observation can be explained by competition between the S_Ni and the S_N1 mechanisms, leading to the retention of stereochemistry. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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12 pages, 4257 KiB

Open AccessArticle

Measuring Bismuth Oxide Particle Size and Morphology in Film-Coated Tablets

by Stefani Fertaki, Georgios Bagourakis, Malvina Orkoula and Christos Kontoyannis

Molecules 2022, 27(8), 2602; https://doi.org/10.3390/molecules27082602 - 18 Apr 2022

Cited by 1 | Viewed by 2310

Abstract

The assessment of active pharmaceutical ingredient (API) particle size and morphology is of great importance for the pharmaceutical industry since it is expected to significantly affect physicochemical properties. However, very few methods are published for the determination of API morphology and particle size [...] Read more.

The assessment of active pharmaceutical ingredient (API) particle size and morphology is of great importance for the pharmaceutical industry since it is expected to significantly affect physicochemical properties. However, very few methods are published for the determination of API morphology and particle size of film-coated (FC) tablets. In the current study we provide a methodology for the measurement of API particle size and morphology which could be applied in several final products. Bismuth Oxide 120 mg FC Tabs were used for our method development, which contain bismuth oxide (as tripotassium dicitratobismuthate (bismuth subcitrate)) as the active substance. The sample preparation consists of partial excipient dissolution in different solvents. Following this procedure, the API particles were successfully extracted from the granules. Particle size and morphology identification in Bismuth Oxide 120 mg FC Tabs was conducted using micro-Raman mapping spectroscopy and ImageJ software. The proposed methodology was repeated for the raw API material and against a reference listed drug (RLD) for comparative purposes. The API particle size was found to have decreased compared to the raw API, while the API morphology was also affected from the formulation manufacturing process. Comparison with the RLD product also revealed differences, mainly in the API particle size and secondarily in the crystal morphology. Full article

(This article belongs to the Special Issue Sample Preparation-Quo Vadis: Current Status of Sample Preparation Approaches-2nd Edition)

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18 pages, 3314 KiB

Open AccessArticle

Computational Insights and In Vitro Validation of Antibacterial Potential of Shikimate Pathway-Derived Phenolic Acids as NorA Efflux Pump Inhibitors

by Karishma Singh, Roger M. Coopoosamy, Njabulo J. Gumede and Saheed Sabiu

Molecules 2022, 27(8), 2601; https://doi.org/10.3390/molecules27082601 - 18 Apr 2022

Cited by 10 | Viewed by 2473

Abstract

The expression of the efflux pump systems is the most important mechanism of antibiotic resistance in bacteria, as it contributes to reduced concentration and the subsequent inactivity of administered antibiotics. NorA is one of the most studied antibacterial targets used as a model [...] Read more.

The expression of the efflux pump systems is the most important mechanism of antibiotic resistance in bacteria, as it contributes to reduced concentration and the subsequent inactivity of administered antibiotics. NorA is one of the most studied antibacterial targets used as a model for efflux-mediated resistance. The present study evaluated shikimate pathway-derived phenolic acids against NorA (PDB ID: 1PW4) as a druggable target in antibacterial therapy using in silico modelling and in vitro methods. Of the 22 compounds evaluated, sinapic acid (−9.0 kcal/mol) and p-coumaric acid (−6.3 kcal/mol) had the best and most prominent affinity for NorA relative to ciprofloxacin, a reference standard (−4.9 kcal/mol). A further probe into the structural stability and flexibility of the resulting NorA-phenolic acids complexes through molecular dynamic simulations over a 100 ns period revealed p-coumaric acid as the best inhibitor of NorA relative to the reference standard. In addition, both phenolic acids formed H-bonds with TYR 76, a crucial residue implicated in NorA efflux pump inhibition. Furthermore, the phenolic acids demonstrated favourable drug likeliness and conformed to Lipinski’s rule of five for ADME properties. For the in vitro evaluation, the phenolic acids had MIC values in the range 31.2 to 62.5 μg/mL against S. aureus, and E. coli, and there was an overall reduction in MIC following their combination with ciprofloxacin. Taken together, the findings from both the in silico and in vitro evaluations in this study have demonstrated high affinity of p-coumaric acid towards NorA and could be suggestive of its exploration as a novel NorA efflux pump inhibitor. Full article

(This article belongs to the Topic Novel Antimicrobial Agents: Discovery, Design and New Therapeutic Strategies)

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11 pages, 1111 KiB

Open AccessArticle

Green Strategies for the Preparation of Enantiomeric 5–8-Membered Carbocyclic β-Amino Acid Derivatives through CALB-Catalyzed Hydrolysis

by Sayeh Shahmohammadi, Tünde Faragó, Márta Palkó and Enikő Forró

Molecules 2022, 27(8), 2600; https://doi.org/10.3390/molecules27082600 - 18 Apr 2022

Cited by 3 | Viewed by 2290

Abstract

Candida antarctica lipase B-catalyzed hydrolysis of carbocyclic 5–8-membered cis β-amino esters was carried out in green organic media, under solvent-free and ball-milling conditions. In accordance with the high enantioselectivity factor (E > 200) observed in organic media, the preparative-scale resolutions of β-amino [...] Read more.

Candida antarctica lipase B-catalyzed hydrolysis of carbocyclic 5–8-membered cis β-amino esters was carried out in green organic media, under solvent-free and ball-milling conditions. In accordance with the high enantioselectivity factor (E > 200) observed in organic media, the preparative-scale resolutions of β-amino esters were performed in tBuOMe at 65 °C. The unreacted β-amino ester enantiomers (1R,2S) and product β-amino acid enantiomers (1S,2R) were obtained with modest to excellent enantiomeric excess (ee) values (ee_s > 62% and ee_p > 96%) and in good chemical yields (>25%) in one or two steps. The enantiomers were easily separated by organic solvent/H₂O extraction. Full article

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22 pages, 6634 KiB

Open AccessArticle

Synthesis of New Phenolic Derivatives of Quinazolin-4(3H)-One as Potential Antioxidant Agents—In Vitro Evaluation and Quantum Studies

by Raluca Pele, Gabriel Marc, Anca Stana, Ioana Ionuț, Cristina Nastasă, Brîndușa Tiperciuc, Ilioara Oniga, Adrian Pîrnău, Laurian Vlase and Ovidiu Oniga

Molecules 2022, 27(8), 2599; https://doi.org/10.3390/molecules27082599 - 18 Apr 2022

Cited by 8 | Viewed by 3487

Abstract

Considering the important damage caused by the reactive oxygen (ROS) and nitrogen (RNS) species in the human organism, the need for new therapeutic agents, with superior efficacy to the known natural and synthetic antioxidants, is crucial. Quinazolin-4-ones are known for their wide range [...] Read more.

Considering the important damage caused by the reactive oxygen (ROS) and nitrogen (RNS) species in the human organism, the need for new therapeutic agents, with superior efficacy to the known natural and synthetic antioxidants, is crucial. Quinazolin-4-ones are known for their wide range of biological activities, and phenolic compounds display an important antioxidant effect. Linking the two active pharmacophores may lead to an increase of the antioxidant activity. Therefore, we synthesized four series of new hybrid molecules bearing the quinazolin-4-one and phenol scaffolds. Their antioxidant potential was evaluated in vitro, considering different possible mechanisms of action: hydrogen atom transfer, ability to donate electrons and metal ions chelation. Theoretical quantum and thermodynamical calculations were also performed. Some compounds, especially the ortho diphenolic ones, exerted a stronger antioxidant effect than ascorbic acid and Trolox. Full article

(This article belongs to the Collection Early-Career Researchers in Chemistry)

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39 pages, 13554 KiB

Open AccessReview

Synthetic Approaches to Biologically Active C-2-Substituted Benzothiazoles

by Bagrat A. Shainyan, Larisa V. Zhilitskaya and Nina O. Yarosh

Molecules 2022, 27(8), 2598; https://doi.org/10.3390/molecules27082598 - 18 Apr 2022

Cited by 10 | Viewed by 4457

Abstract

Numerous benzothiazole derivatives are used in organic synthesis, in various industrial and consumer products, and in drugs, with a wide spectrum of biological activity. As the properties of the benzothiazole moiety are strongly affected by the nature and position of substitutions, in this [...] Read more.

Numerous benzothiazole derivatives are used in organic synthesis, in various industrial and consumer products, and in drugs, with a wide spectrum of biological activity. As the properties of the benzothiazole moiety are strongly affected by the nature and position of substitutions, in this review, covering the literature from 2016, we focus on C-2-substituted benzothiazoles, including the methods of their synthesis, structural modification, reaction mechanisms, and possible pharmacological activity. The synthetic approaches to these heterocycles include both traditional multistep reactions and one-pot atom economy processes using green chemistry principles and easily available reagents. Special attention is paid to the methods of the thiazole ring closure and chemical modification by the introduction of pharmacophore groups. Full article

(This article belongs to the Special Issue Feature Papers in Organic Chemistry)

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16 pages, 3486 KiB

Open AccessArticle

Explorations on Thermodynamic and Kinetic Performances of Various Cationic Exchange Durations for Synthetic Clinoptilolite

by Keling Wang, Bingying Jia, Yehong Li, Jihong Sun and Xia Wu

Molecules 2022, 27(8), 2597; https://doi.org/10.3390/molecules27082597 - 18 Apr 2022

Cited by 3 | Viewed by 1683

Abstract

Various cation–exchanged clinoptilolites (M–CPs, M = Li⁺, Cs⁺, Ca²⁺, Sr²⁺) were prepared, and their exchanged thermodynamic (and kinetic) properties and adsorption performances for CH₄, N₂, and CO₂ were investigated. The [...] Read more.

Various cation–exchanged clinoptilolites (M–CPs, M = Li⁺, Cs⁺, Ca²⁺, Sr²⁺) were prepared, and their exchanged thermodynamic (and kinetic) properties and adsorption performances for CH₄, N₂, and CO₂ were investigated. The results demonstrated that the relative crystallinity of M–CP_S decreased with the increase of exchange times. Their chemisorbed water weight loss gradually increased with the increasing exchange times, except that of Cs–x–CP. The Δ_r

G_{m}^{θ}

values of exchange process of Li⁺, Cs⁺, Ca²⁺, or Sr² presented the increased trend with the enhanced exchange times, but they decreased as the temperature increased. The negative Δ_r

G_{m}^{θ}

values and the positive Δ_r

H_{m}^{θ}

and Δ_r

S_{m}^{θ}

values suggested that the exchanged procedure belonged to spontaneous, endothermic, and entropy-increasing behaviors; their kinetic performances followed a pseudo–second–order model. However, the calculated E_a values of exchange process showed the increased tendencies with the enhanced exchange times, indicating that the exchange process became more difficult. Finally, the preliminary adsorption results indicated that the maximum adsorption amount at 273 K and 1 bar was 0.51 mmol/g of CH₄ and 0.38 mmol/g of N₂ by (Na, K)–CP, and 2.32 mmol/g of CO₂ by Li–6–CP. Full article

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16 pages, 2126 KiB

Open AccessArticle

A Novel Distachionate from Breynia distachia Treats Inflammations by Modulating COX-2 and Inflammatory Cytokines in Rat Liver Tissue

by Malik Saadullah, Muhammad Asif, Arshad Farid, Faiza Naseem, Sheikh Abdur Rashid, Shakira Ghazanfar, Muhammad Muzammal, Sohail Ahmad, Yousef A. Bin Jardan, Huda Alshaya, Muhammad Hamzah Saleem, Shafaqat Ali, Charles Oluwaseun Adetunji and Sania Arif

Molecules 2022, 27(8), 2596; https://doi.org/10.3390/molecules27082596 - 18 Apr 2022

Cited by 22 | Viewed by 2568

Abstract

Breynia distachia is a plant of genus Breynia belonging to family Phyllanthaceae. This study was conducted to isolate and examine the anti-inflammatory attributes of the roots of Breynia distachia. Methanol extract from roots were prepared by simple maceration. For phytochemical studies, isolation, [...] Read more.

Breynia distachia is a plant of genus Breynia belonging to family Phyllanthaceae. This study was conducted to isolate and examine the anti-inflammatory attributes of the roots of Breynia distachia. Methanol extract from roots were prepared by simple maceration. For phytochemical studies, isolation, purification, structure elucidation, metal analysis, total phenolic content, and solubility test were done by chromatographic and spectroscopic techniques. Anti-inflammatory activity was evaluated by cotton pallet edema model and carrageenan paw edema model, and antioxidant potential was evaluated by DPPH, FRAP, and ABTS antioxidants assays. Metal analysis of BD.Me revealed the presence of Na > Mg > K > Mn > Fe = Zn in respective order. Four phytochemicals such as gallic acid, quercetin, sinapic acid, and p-coumaric acid are found in Breynia distachia. Quercetin is present in relatively larger quantity, and shows antioxidant activity by reducing the ferric iron to ferrous iron. Novel distachionate shows high antioxidant activity in ABTS assay by reducing reactive oxygen species. Quantitative or qualitative analysis performed by HPLC indicates the ascending peaks or presence of secondary products (metabolites) respectively. Histopathology analysis of liver, spleen, heart, and kidney was done, revealing mild inflammations in spleen and liver, and no cytotoxicity in heart and kidney. Oral administration of BD.Me and ditachionate significantly inhibits the carrageenan and cotton pellet-induced paw edema in 1st and 2nd h with (ns = p > 0.05) than control. After 3rd, 4th, 5th, and 6th h, BD.Me and ditachionate showed inhibition of paw edema in a highly significant (*** = p < 0.001) manner as compared to control. In cotton-pellet edema model, distachionate shows a %inhibition of 57.3% at a dose level of 5 mg/kg. Docking values obtained from distachionate-COX-2 complex suggest a potent inhibitor evaluated for this protein. The distachionate shows effective anti-inflammatory activity. Methanol extracts of roots showed significant lipoxygenase inhibitory activity by IC₅₀ values of 155.7 ± 0.55 and 132.9 ± 0.33 μg/mL. Data from various in vitro and in vivo models suggest that novel distachionate isolated from Breynia distachia shows strong antioxidant and anti-inflammatory activities; it should be further studied for the exploration of its medicinal potential. Full article

(This article belongs to the Special Issue Bioactive Molecules Targeting Inflammation and Oxidative Stress Processes in Related Diseases)

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19 pages, 1057 KiB

Open AccessArticle

Impacts of Gum Arabic and Polyvinylpyrrolidone (PVP) with Salicylic Acid on Peach Fruit (Prunus persica) Shelf Life

by Mohamed A. Taher, A. A. Lo’ay, Mostafa Gouda, Safaa A. Limam, Mohamed F. M. Abdelkader, Samah O. Osman, Mohammad Fikry, Esmat F. Ali, Sayed. Y. Mohamed, Hoda A. Khalil, Diaa O. El-Ansary, Sherif F. El-Gioushy, Hesham S. Ghazzawy, Aly M. Ibrahim, Mahmoud F. Maklad, Mohamed A. Abdein and Dalia M. Hikal

Molecules 2022, 27(8), 2595; https://doi.org/10.3390/molecules27082595 - 18 Apr 2022

Cited by 19 | Viewed by 3382

Abstract

Peaches are grown in many Egyptian orchards for local and global fresh market sales. The interior fruit tissue breakdown (IFTB), often resulting in decayed peaches, is a severe problem during marketing. Therefore, to minimize FTB of peaches, in this study, gum arabic (GA) [...] Read more.

Peaches are grown in many Egyptian orchards for local and global fresh market sales. The interior fruit tissue breakdown (IFTB), often resulting in decayed peaches, is a severe problem during marketing. Therefore, to minimize FTB of peaches, in this study, gum arabic (GA) and polyvinylpyrrolidone (PVP) were mixed with different concentrations of salicylic acid (SA) (0, 1, and 2 mM) and were applied as edible coating to extend the shelf life of peach fruits. Mature peaches were selected and harvested when peaches reached total soluble solid content (SSC: 8.5%) and fruit firmness of about 47 N. Fruits were coated and stored at room temperature (26 ± 1 °C and air humidity 51 ± 1%) for 10 days during two seasons: 2020 and 2021. Fruit coated with GA/PVP-SA 2 mM showed a significant (p < 0.05) inhibition in degrading enzyme activities (CWDEs), such as lipoxygenase (LOX), cellulase (CEL), and pectinase (PT), compared to uncoated and coated fruits during the shelf-life period. Hence, cell wall compartments were maintained. Consequently, there was a reduction in browning symptoms in fruits by inhibiting polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL) activities. Thus, the fruit skin browning index showed almost no symptoms. The lipid peroxidation process and ionic permeability declined as well. The result suggests that, by applying GA/PVP-SA 2 mM as an edible coating, fruit tissue breakdown can be minimized, and the shelf life of peach can be extended up to 10 days without symptoms of tissue breakdown. Full article

(This article belongs to the Special Issue State of the Art of Natural Antioxidants: Extraction, Detection and Biofunctions)

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27 pages, 7017 KiB

Open AccessArticle

The Biological Fate of a Novel Anticancer Drug Candidate TNBG-5602: Metabolic Profile, Interaction with CYP450, and Pharmacokinetics in Rats

by Rui Li, Sha Zhou, Zongjie Gan, Lijuan Wang and Yu Yu

Molecules 2022, 27(8), 2594; https://doi.org/10.3390/molecules27082594 - 18 Apr 2022

Cited by 2 | Viewed by 2124

Abstract

TNBG-5602, a novel anticancer drug candidate, may induce the expression of PPARγ, causing targeted lipotoxicity in cancer tissues. In this study, the in vivo metabolism in rats, in vitro metabolism in recombinant cytochromes, molecular docking for the CYP binding site, and pharmacokinetics in [...] Read more.

TNBG-5602, a novel anticancer drug candidate, may induce the expression of PPARγ, causing targeted lipotoxicity in cancer tissues. In this study, the in vivo metabolism in rats, in vitro metabolism in recombinant cytochromes, molecular docking for the CYP binding site, and pharmacokinetics in rats were explored to better understand TNBG-5602′s in vivo fate and behavior. Thirteen metabolites were identified using a high-resolution mass spectrometry method, and metabolizing pathways of TNBG-5602 were proposed. Results suggest that TNBG-5602 could be metabolized by CYP450s, while CYP2D6 may play an important role in its in vivo metabolism. The main metabolizing sites of TNBG-5602 are the amino group on the side chain and rings A and E in the molecule. TNBG-5602 is a potent CYP2D6 inhibitor, with an IC₅₀ value of 2.52 μM. An interaction responsible for its metabolism is formed by the NH on the side chain bonding with the ASP301 on the CYP2D6. The pharmacokinetics in rats after a single intravenous administration were fitted to a two-compartment model. The clearance was 0.022 L min⁻¹, and the elimination half-life was 710.9 min. The distribution volume of the peripheral compartment was 1.88-fold that of the central compartment, while the K₁₂ was 1.5-fold that of K₂₁. In conclusion, these studies have not only revealed the metabolizing pathways of TNBG-5602 using in vivo and in vitro methodology, but they have also provided the pharmacokinetic characteristics of TNBG-5602 in rats. The results suggest that TNBG-5602 has good drug developability in terms of pharmacokinetic behaviors. Full article

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22 pages, 4505 KiB

Open AccessArticle

Suppression of Oxidative Stress and Proinflammatory Cytokines Is a Potential Therapeutic Action of Ficus lepicarpa B. (Moraceae) against Carbon Tetrachloride (CCl₄)-Induced Hepatotoxicity in Rats

by Senty Vun-Sang, Kenneth Francis Rodrigues, Urban J. A. Dsouza and Mohammad Iqbal

Molecules 2022, 27(8), 2593; https://doi.org/10.3390/molecules27082593 - 18 Apr 2022

Cited by 2 | Viewed by 2434

Abstract

Local tribes use the leaves of Ficus lepicarpa B. (Moraceae), a traditional Malaysian medicine, as a vegetable dish, a tonic, and to treat ailments including fever, jaundice and ringworm. The purpose of this study was to look into the possible therapeutic effects of [...] Read more.

Local tribes use the leaves of Ficus lepicarpa B. (Moraceae), a traditional Malaysian medicine, as a vegetable dish, a tonic, and to treat ailments including fever, jaundice and ringworm. The purpose of this study was to look into the possible therapeutic effects of F. lepicarpa leaf extract against carbon tetrachloride (CCl₄)-induced liver damage in rats. The DPPH test was used to measure the antioxidant activity of plants. Gas chromatography-mass spectrometry was used for the phytochemical analysis (GCMS). Six groups of male Sprague-Dawley rats were subjected to the following treatment regimens: control group, CCl₄ alone, F. lepicarpa 400 mg/kg alone, CCl₄ + F. lepicarpa 100 mg/kg, CCl₄ + F. lepicarpa 200 mg/kg and CCl₄ + F. lepicarpa 400 mg/kg. The rats were euthanized after two weeks, and biomarkers of liver function and antioxidant enzyme status were assessed. To assess the extent of liver damage and fibrosis, histopathological and immunohistochemical examinations of liver tissue were undertaken. The total phenolic content and the total flavonoid content in methanol extract of F. lepicarpa leaves were 58.86 ± 0.04 mg GAE/g and 44.31 ± 0.10 mg CAE/g, respectively. F. lepicarpa’s inhibitory concentration (IC₅₀) for free radical scavenging activity was reported to be 3.73 mg/mL. In a dose-related manner, F. lepicarpa was effective in preventing an increase in serum ALT, serum AST and liver MDA. Histopathological alterations revealed that F. lepicarpa protects against the oxidative stress caused by CCl₄. The immunohistochemistry results showed that proinflammatory cytokines (tumour necrosis factor-α, interleukin-6, prostaglandin E₂) were suppressed. The antioxidative, anti-inflammatory, and free-radical scavenging activities of F. lepicarpa can be related to its hepatoprotective benefits. Full article

(This article belongs to the Special Issue Experimental and Theoretical Researches on Hazardous Chemicals: Detection, Protection, and Decontamination)

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16 pages, 2846 KiB

Open AccessArticle

Electrochemical Determination of Nanoparticle Size: Combined Theoretical and Experimental Study for Matrixless Silver Nanoparticles

by Monika Adamowska, Bartosz Pałuba and Wojciech Hyk

Molecules 2022, 27(8), 2592; https://doi.org/10.3390/molecules27082592 - 18 Apr 2022

Viewed by 2176

Abstract

A chronoamperometric procedure for the preparation of silver nanoparticles (AgNPs) in aqueous systems with no extra added stabilizing agents is presented. The uniqueness of the prepared nanoparticle systems was explored by theoretical considerations. The proposed theoretical model predicts the structural parameters of the [...] Read more.

A chronoamperometric procedure for the preparation of silver nanoparticles (AgNPs) in aqueous systems with no extra added stabilizing agents is presented. The uniqueness of the prepared nanoparticle systems was explored by theoretical considerations. The proposed theoretical model predicts the structural parameters of the obtained nanoparticle system. The parameters required for the calculations (the zeta potential, conductivity, and effective diffusion coefficient of ionic silver) are available from independently performed measurements. Chronoamperometry at a microelectrode was employed for the evaluation of the effective diffusion coefficient of ionic silver present in the AgNP solution. The values of AgNP radii predicted by the theoretical model for the selected samples were compared to those obtained by Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) methods. Because of the high polydispersity of the prepared nanoparticle samples, DLS results were overestimated in comparison to both: the TEM results and some theoretical predictions. By correcting the theoretical predictions by the Debye length, the calculated nanoparticle sizes become comparable (within their expanded uncertainties) to those measured in TEM images, especially for the nanosystems at early stages of their formation via the electrosynthesis process. Full article

(This article belongs to the Section Electrochemistry)

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17 pages, 5107 KiB

Open AccessArticle

The Main Structural Unit Elucidation and Immunomodulatory Activity In Vitro of a Selenium-Enriched Polysaccharide Produced by Pleurotus ostreatus

by De Wang, Jiahui Wang, Hui Liu, Meng Liu, Yanjing Yang and Shian Zhong

Molecules 2022, 27(8), 2591; https://doi.org/10.3390/molecules27082591 - 18 Apr 2022

Cited by 12 | Viewed by 2234

Abstract

In recent years, the structure of selenium-enriched polysaccharides and their application in immunomodulation have attracted much attention. In previous studies, we extracted and purified a novel selenium-enriched Pleurotus ostreatus polysaccharide called Se-POP-21, but its structure and immunomodulatory activity were still unclear. In this [...] Read more.

In recent years, the structure of selenium-enriched polysaccharides and their application in immunomodulation have attracted much attention. In previous studies, we extracted and purified a novel selenium-enriched Pleurotus ostreatus polysaccharide called Se-POP-21, but its structure and immunomodulatory activity were still unclear. In this study, the main structural unit formula of Se-POP-21 was characterized by methylation analysis and an NMR experiment. The results showed that the backbone of Se-POP-21 was →[2,6)-α-D-Galp-(1→6)-α-D-Galp-(1]₄→2,4)-β-L-Arap-(1→[2,6)-α-D-Galp-(1→6)-α-D-Galp-(1]₄→, branched chain of β-D-Manp-(1→ and β-D-Manp-(1→4)-β-L-Arap-(1→ connected with →2,6)-α-D-Galp-(1→ and →2,4)-β-L-Arap-(1→,respectively, through the O-2 bond. In vitro cell experiments indicated that Se-POP-21 could significantly enhance the proliferation and phagocytosis of RAW264.7 cells, upregulate the expression of costimulatory molecules CD80/CD86, and promote RAW264.7 cells to secrete NO, ROS, TNF-α, IL-1β, and IL-6 by activating the NF-κB protein. The results of this study indicate that Se-POP-21 can effectively activate RAW264.7 cells. Thus, it has the potential to be used in immunomodulatory drugs or functional foods. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Sources: Characterization and Biological Evaluation)

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18 pages, 9337 KiB

Open AccessArticle

Doxorubicin-Conjugated Zinc Oxide Nanoparticles, Biogenically Synthesised Using a Fungus Aspergillus niger, Exhibit High Therapeutic Efficacy against Lung Cancer Cells

by Prakriti Mishra, Afza Ahmad, Lamya Ahmed Al-Keridis, Nawaf Alshammari, Nadiyah M. Alabdallah, Khursheed Muzammil, Mohd Saeed and Irfan Ahmad Ansari

Molecules 2022, 27(8), 2590; https://doi.org/10.3390/molecules27082590 - 18 Apr 2022

Cited by 18 | Viewed by 2791

Abstract

This study reports the therapeutic effectiveness of doxorubicin-conjugated zinc oxide nanoparticles against lung cancer cell line. The zinc oxide nanoparticles (ZnONPs) were first synthesised using a fungus, isolated from air with an extraordinary capability to survive in very high concentrations of zinc salt. [...] Read more.

This study reports the therapeutic effectiveness of doxorubicin-conjugated zinc oxide nanoparticles against lung cancer cell line. The zinc oxide nanoparticles (ZnONPs) were first synthesised using a fungus, isolated from air with an extraordinary capability to survive in very high concentrations of zinc salt. Molecular analysis based on 18S rRNA gene sequencing led to its identification as Aspergillus niger with the NCBI accession no. OL636020. The fungus was found to produce ZnONPs via the reduction of zinc ions from zinc sulphate. The ZnONPs were characterised by various biophysical techniques. ZnONPs were further bioconjugated with the anti-cancer drug doxorubicin (DOX), which was further confirmed by different physical techniques. Furthermore, we examined the cytotoxic efficacy of Doxorubicin-bioconjugated-ZnONPs (DOX-ZnONPs) against lung cancer A549 cells in comparison to ZnONPs and DOX alone. The cytotoxicity caused due to ZnONPs, DOX and DOX-ZnONPs in lung cancer A549 cells was assessed by MTT assay. DOX-ZnONPs strongly inhibited the proliferation of A549 with IC50 value of 0.34 μg/mL, which is lower than IC50 of DOX alone (0.56 μg/mL). Moreover, DOX-ZnONPs treated cells also showed increased nuclear condensation, enhanced ROS generation in cytosol and reduced mitochondrial membrane potential. To investigate the induction of apoptosis, caspase-3 activity was measured in all the treated groups. Conclusively, results of our study have established that DOX-ZnONPs have strong therapeutic efficacy to inhibit the growth of lung cancer cells in comparison to DOX alone. Our study also offers substantial evidence for the biogenically synthesised zinc oxide nanoparticle as a promising candidate for a drug delivery system. Full article

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14 pages, 4198 KiB

Open AccessArticle

A Comprehensive Investigation of Interactions between Antipsychotic Drug Quetiapine and Human Serum Albumin Using Multi-Spectroscopic, Biochemical, and Molecular Modeling Approaches

by Seema Zargar, Tanveer A. Wani, Nawaf A. Alsaif and Arwa Ishaq A. Khayyat

Molecules 2022, 27(8), 2589; https://doi.org/10.3390/molecules27082589 - 18 Apr 2022

Cited by 46 | Viewed by 2558

Abstract

Quetiapine (QTP) is a short-acting atypical antipsychotic drug that treats schizophrenia or manic episodes of bipolar disorder. Human serum albumin (HSA) is an essential transport protein that transports hormones and various other ligands to their intended site of action. The interactions of QTP [...] Read more.

Quetiapine (QTP) is a short-acting atypical antipsychotic drug that treats schizophrenia or manic episodes of bipolar disorder. Human serum albumin (HSA) is an essential transport protein that transports hormones and various other ligands to their intended site of action. The interactions of QTP with HSA and their binding mechanism in the HSA-QTP system was studied using spectroscopic and molecular docking techniques. The UV-Vis absorption study shows hyperchromicity in the spectra of HSA on the addition of QTP, suggesting the complex formation and interactions between QTP and HSA. The results of intrinsic fluorescence indicate that QTP quenched the fluorescence of HSA and confirmed the complex formation between HSA and QTP, and this quenching mechanism was a static one. Thermodynamic analysis of the HSA-QTP system confirms the involvement of hydrophobic forces, and this complex formation is spontaneous. The competitive displacement and molecular docking experiments demonstrated that QTP is preferentially bound to HSA subdomain IB. Furthermore, the CD experiment results showed conformational changes in the HSA-QTP system. Besides this, the addition of QTP does not affect the esterase-like activity of HSA. This study will help further understand the credible mechanism of transport and delivery of QTP via HSA and design new QTP-based derivatives with greater efficacy. Full article

(This article belongs to the Section Photochemistry)

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13 pages, 657 KiB

Open AccessArticle

Characterization of Primary Action Mode of Eight Essential Oils and Evaluation of Their Antibacterial Effect against Extended-Spectrum β-Lactamase (ESBL)-Producing Escherichia coli Inoculated in Turkey Meat

by Chedia Aouadhi, Ahlem Jouini, Dhekra Mechichi, Mouna Boulares, Safa Hamrouni and Abderrazak Maaroufi

Molecules 2022, 27(8), 2588; https://doi.org/10.3390/molecules27082588 - 18 Apr 2022

Cited by 7 | Viewed by 2463

Abstract

The current study aims to evaluate the antimicrobial activity of eight essential oils (EOs) against multidrug-resistant Escherichia coli strains, producing extended-spectrum β-lactamase (ESBL) enzymes and isolated from foods. Disc-diffusion assay showed that the inhibition diameters generated by EOs varied significantly among the tested [...] Read more.

The current study aims to evaluate the antimicrobial activity of eight essential oils (EOs) against multidrug-resistant Escherichia coli strains, producing extended-spectrum β-lactamase (ESBL) enzymes and isolated from foods. Disc-diffusion assay showed that the inhibition diameters generated by EOs varied significantly among the tested EOs and strains. In fact, EOs extracted from Thymus capitaus, Eucalyptus camaldulensis, Trachyspermum ammi and Mentha pulegium exerted an important antimicrobial effect against tested strains, with the diameters of inhibition zones varied between 20 and 27 mm. Moreover, minimal inhibition and bactericidal concentration (MIC and MBC) values demonstrated that T. capitatus EOs generate the most important inhibitory effect against E. coli strains, with MIC values ranging from 0.02 to 0.78%. Concerning the mode of action of T. capitatus EO, the obtained data showed that treatment with this EO at its MIC reduced the viability of E. coli strains, their tolerance to NaCl and promoted the loss of 260-nm-absorbing material. In addition, in the presence of T. capitatus EO, cells became disproportionately sensitive to subsequent autolysis. Moreover, the inhibitory effect of T. capitatus was evaluated against two E. coli strains, experimentally inoculated (10⁵ CFU/g) in minced turkey meat, in the presence of two different concentrations of EO (MIC and 2 × MIC), and stored for 15 days. In both samples, EO exerted a bacteriostatic effect in the presence of concentrations equal to MIC. Interestingly, at 2 × CMI concentration, the bactericidal activity was pronounced after 15 days of storage. Our results highlighted that the use of essential oils, specially of T. capitatus, to inhibit or prevent the growth of extended-spectrum β-lactamase (ESBL)-producing E. coli in food, may be a promising alternative to chemicals. Full article

(This article belongs to the Special Issue Exploration of Natural Compounds: Pharmaceutical, Phytochemical and Biological Analysis)

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9 pages, 2164 KiB

Open AccessCommunication

Determination of Brain Tissue Samples Storage Conditions for Reproducible Intraoperative Lipid Profiling

by Stanislav I. Pekov, Evgeny S. Zhvansky, Vasily A. Eliferov, Anatoly A. Sorokin, Daniil G. Ivanov, Eugene N. Nikolaev and Igor A. Popov

Molecules 2022, 27(8), 2587; https://doi.org/10.3390/molecules27082587 - 18 Apr 2022

Cited by 3 | Viewed by 1991

Abstract

Ex-vivo molecular profiling has recently emerged as a promising method for intraoperative tissue identification, especially in neurosurgery. The short-term storage of resected samples at room temperature is proposed to have negligible influence on the lipid molecular profiles. However, a detailed investigation of short-term [...] Read more.

Ex-vivo molecular profiling has recently emerged as a promising method for intraoperative tissue identification, especially in neurosurgery. The short-term storage of resected samples at room temperature is proposed to have negligible influence on the lipid molecular profiles. However, a detailed investigation of short-term molecular profile stability is required to implement molecular profiling in a clinic. This study evaluates the effect of storage media, temperature, and washing solution to determine conditions that provide stable and reproducible molecular profiles, with the help of ambient ionization mass spectrometry using rat cerebral cortex as model brain tissue samples. Utilizing normal saline for sample storage and washing media shows a positive effect on the reproducibility of the spectra; however, the refrigeration shows a negligible effect on the spectral similarity. Thus, it was demonstrated that up to hour-long storage in normal saline, even at room temperature, ensures the acquisition of representative molecular profiles using ambient ionization mass spectrometry. Full article

(This article belongs to the Special Issue Mass Spectrometry in the Health Sciences)

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45 pages, 11031 KiB

Open AccessReview

Covalent Organic Frameworks for Chemical and Biological Sensing

by Shiji Zhang, Danqing Liu and Guangtong Wang

Molecules 2022, 27(8), 2586; https://doi.org/10.3390/molecules27082586 - 18 Apr 2022

Cited by 30 | Viewed by 6077

Abstract

Covalent organic frameworks (COFs) are a class of crystalline porous organic polymers with polygonal porosity and highly ordered structures. The most prominent feature of the COFs is their excellent crystallinity and highly ordered modifiable one-dimensional pores. Since the first report of them in [...] Read more.

Covalent organic frameworks (COFs) are a class of crystalline porous organic polymers with polygonal porosity and highly ordered structures. The most prominent feature of the COFs is their excellent crystallinity and highly ordered modifiable one-dimensional pores. Since the first report of them in 2005, COFs with various structures were successfully synthesized and their applications in a wide range of fields including gas storage, pollution removal, catalysis, and optoelectronics explored. In the meantime, COFs also exhibited good performance in chemical and biological sensing, because their highly ordered modifiable pores allowed the selective adsorption of the analytes, and the interaction between the analytes and the COFs’ skeletons may lead to a detectable change in the optical or electrical properties of the COFs. In this review, we firstly demonstrate the basic principles of COFs-based chemical and biological sensing, then briefly summarize the applications of COFs in sensing some substances of practical value, including some gases, ions, organic compounds, and biomolecules. Finally, we discuss the trends and the challenges of COFs-based chemical and biological sensing. Full article

(This article belongs to the Special Issue Potential Applications of Functional Porous Organic Frameworks)

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26 pages, 401 KiB

Open AccessReview

Recent Advances in the Antiproliferative and Proapoptotic Activity of Various Plant Extracts and Constituents against Murine Malignant Melanoma

by Daria-Antonia Dumitraș and Sanda Andrei

Molecules 2022, 27(8), 2585; https://doi.org/10.3390/molecules27082585 - 17 Apr 2022

Cited by 11 | Viewed by 3272

Abstract

Although conventional medicine, chemical drug synthesis and pharmaceutical research are advancing at a rapid pace, nature remains a major supplier of biological molecules. Natural bioactive compounds are studied closely especially as an alternative to the limitations of conventional therapy in many diseases, melanoma [...] Read more.

Although conventional medicine, chemical drug synthesis and pharmaceutical research are advancing at a rapid pace, nature remains a major supplier of biological molecules. Natural bioactive compounds are studied closely especially as an alternative to the limitations of conventional therapy in many diseases, melanoma being one of them. Malignant melanoma is a highly aggressive type of cancer, and the current methods of treatment used are cryotherapy, external surgery, radiation therapy, chemotherapy, photodynamic therapy, biological therapy, and targeted drug therapy. Unfortunately, these treatment methods are often inefficient, extremely expensive and cause many side effects, which is why focusing on melanoma chemoprevention and adjuvant therapy with natural herbal phytoconstituents is an emerging strategy to prevent, cure or treat melanoma. This review aims to examine the latest discoveries in terms of potential natural bioactive compounds that possess important activity against the development and spread of murine melanoma cancer. In particular, the use of different phytochemicals such as phenolic acids, flavonoids, anthocyanins, terpenoids, essential oils and carotenoids in vitro and in vivo models will be discussed. These data are helpful in guiding researchers in the direction of studying phytonutrients with important effects in the prevention and treatment of melanoma. Full article

(This article belongs to the Special Issue Anti-tumor Effects of Natural Products on Tumor Itself and Tumor Microenvironments)

17 pages, 2483 KiB

Open AccessArticle

Hydrogen Bonding in the Dimer and Monohydrate of 2-Adamantanol: A Test Case for Dispersion-Corrected Density Functional Methods

by Marcos Juanes, Rizalina Tama Saragi, Cristóbal Pérez, Luca Evangelisti, Lourdes Enríquez, Martín Jaraíz and Alberto Lesarri

Molecules 2022, 27(8), 2584; https://doi.org/10.3390/molecules27082584 - 17 Apr 2022

Cited by 3 | Viewed by 2698

Abstract

Weakly-bound intermolecular clusters constitute reductionist physical models for non-covalent interactions. Here we report the observation of the monomer, the dimer and the monohydrate of 2-adamantanol, a secondary alcohol with a bulky ten-carbon aliphatic skeleton. The molecular species were generated in a supersonic jet [...] Read more.

Weakly-bound intermolecular clusters constitute reductionist physical models for non-covalent interactions. Here we report the observation of the monomer, the dimer and the monohydrate of 2-adamantanol, a secondary alcohol with a bulky ten-carbon aliphatic skeleton. The molecular species were generated in a supersonic jet expansion and characterized using broadband chirped-pulse microwave spectroscopy in the 2–8 GHz frequency region. Two different gauche-gauche O-H···O hydrogen-bonded isomers were observed for the dimer of 2-adamantanol, while a single isomer was observed for the monomer and the monohydrate. The experimental rotational parameters were compared with molecular orbital calculations using density functional theory (B3LYP-D3(BJ), B2PLYP-D3(BJ), CAM-B3LYP-D3(BJ), ωB97XD), additionally providing energetic and electron density characterization. The shallow potential energy surface makes the dimer an interesting case study to benchmark dispersion-corrected computational methods and conformational search procedures. Full article

(This article belongs to the Special Issue Spectroscopic Characterization of Molecular Clusters and Large Amplitude Motions)

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36 pages, 887 KiB

Open AccessReview

Dioscorea spp.: Comprehensive Review of Antioxidant Properties and Their Relation to Phytochemicals and Health Benefits

by Aušra Adomėnienė and Petras Rimantas Venskutonis

Molecules 2022, 27(8), 2530; https://doi.org/10.3390/molecules27082530 - 17 Apr 2022

Cited by 34 | Viewed by 7058

Abstract

Dioscorea, consisting of over 600 species, is the most important genus in the Dioscoreaceae family; however, the practically used plants, which are commonly called yam, are restricted to a remarkably smaller number of species. Numerous studies have reported the high nutritional value [...] Read more.

Dioscorea, consisting of over 600 species, is the most important genus in the Dioscoreaceae family; however, the practically used plants, which are commonly called yam, are restricted to a remarkably smaller number of species. Numerous studies have reported the high nutritional value of yam, particularly as an alternative source of starch and some important micronutrients. Several Dioscorea species are widely used for various medicinal purposes as well. In many studies, the bioactivities and health benefits of Dioscorea extracts and other preparations have been related to the presence of phytochemicals, which possess antioxidant properties; they are related mainly to radical-scavenging capacity in chemical assays and positive effects on the endogenous antioxidant system in cell-based and in vivo assays. Considering the increasing number of publications on this topic and the absence of comprehensive and focused review papers on antioxidant potential, this article summarizes the results of studies on the antioxidant properties of Dioscorea spp. and their relation to phytochemicals and health benefits. A comprehensive survey of the published articles has revealed that the majority of studies have been performed with plant tubers (rhizomes, roots), while reports on leaves are rather scarce. In general, leaf extracts demonstrated stronger antioxidant potential than tuber preparations. This may be related to the differences in phytochemical composition: saponins, phenanthrenes and, for some pigment-rich species (purple yams), anthocyanins are important constituents in tubers, while phenolic acids and flavonoids are characteristic phytochemicals in the leaves. The review may assist in explaining ethnopharmacological knowledge on the health benefits of Dioscorea plants and their preparations; moreover, it may foster further studies of poorly investigated species, as well as their wider application in developing new functional foods and nutraceuticals. Full article

(This article belongs to the Section Natural Products Chemistry)

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25 pages, 6114 KiB

Open AccessArticle

In Vitro Antioxidant and Anticancer Properties of Various E. senegalensis Extracts

by Souleymane Fofana, Cédric Delporte, Rafaèle Calvo Esposito, Moussa Ouédraogo, Pierre Van Antwerpen, Innocent Pierre Guissou, Rasmané Semdé and Véronique Mathieu

Molecules 2022, 27(8), 2583; https://doi.org/10.3390/molecules27082583 - 16 Apr 2022

Cited by 10 | Viewed by 3508

Abstract

Although Erythrina senegalensis is a plant widely used in traditional medicine in sub-Saharan Africa, its biological properties have been poorly investigated to date. We first characterized by conventional reactions the composition of several stem bark extracts and evaluated in acellular and cellular assays [...] Read more.

Although Erythrina senegalensis is a plant widely used in traditional medicine in sub-Saharan Africa, its biological properties have been poorly investigated to date. We first characterized by conventional reactions the composition of several stem bark extracts and evaluated in acellular and cellular assays their pro- or antioxidant properties supported by their high phenolic and flavonoid content, particularly with the methanolic extract. The pro- or antioxidant effects observed did not correlate with their IC₅₀ concentrations against five cancer cell lines determined by MTT assay. Indeed, the CH₂Cl₂ extract and its ethyl acetate (EtOAc) subfraction appeared more potent although they harbored lower pro- or antioxidant effects. Nevertheless, at equipotent concentration, both extracts induced ER- and mitochondria-derived vacuoles observed by fluorescent microscopy that further led to non-apoptotic cell death. LC coupled to high resolution MS investigations have been performed to identify chemical compounds of the extracts. These investigations highlighted the presence of compounds formerly isolated from E. senegalensis including senegalensein that could be retrieved only in the EtOAc subfraction but also thirteen other compounds, such as 16:3-Glc-stigmasterol and hexadecanoic acid, whose anticancer properties have been previously reported. Nineteen other compounds remain to be identified. In conclusion, E. senegalensis appeared rich in compounds with antioxidant and anticancer properties, supporting its use in traditional practice and its status as a species of interest for further investigations in anticancer drug research. Full article

(This article belongs to the Special Issue Bioactive Compounds and Antioxidant Activity of Extracts from Different Natural Plants)

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12 pages, 2387 KiB

Open AccessArticle

Computational Strategy for Minimizing Mycotoxins in Cereal Crops: Assessment of the Biological Activity of Compounds Resulting from Virtual Screening

by Vessela Atanasova, Emmanuel Bresso, Bernard Maigret, Natalia Florencio Martins and Florence Richard-Forget

Molecules 2022, 27(8), 2582; https://doi.org/10.3390/molecules27082582 - 16 Apr 2022

Cited by 2 | Viewed by 2303

Abstract

Cereal crops are frequently affected by toxigenic Fusarium species, among which the most common and worrying in Europe are Fusarium graminearum and Fusarium culmorum. These species are the causal agents of grain contamination with type B trichothecene (TCTB) mycotoxins. To help reduce [...] Read more.

Cereal crops are frequently affected by toxigenic Fusarium species, among which the most common and worrying in Europe are Fusarium graminearum and Fusarium culmorum. These species are the causal agents of grain contamination with type B trichothecene (TCTB) mycotoxins. To help reduce the use of synthetic fungicides while guaranteeing low mycotoxin levels, there is an urgent need to develop new, efficient and environmentally-friendly plant protection solutions. Previously, F. graminearum proteins that could serve as putative targets to block the fungal spread and toxin production were identified and a virtual screening undertaken. Here, two selected compounds, M1 and M2, predicted, respectively, as the top compounds acting on the trichodiene synthase, a key enzyme of TCTB biosynthesis, and the 24-sterol-C-methyltransferase, a protein involved in ergosterol biosynthesis, were submitted for biological tests. Corroborating in silico predictions, M1 was shown to significantly inhibit TCTB yield by a panel of strains. Results were less obvious with M2 that induced only a slight reduction in fungal biomass. To go further, seven M1 analogs were assessed, which allowed evidencing of the physicochemical properties crucial for the anti-mycotoxin activity. Altogether, our results provide the first evidence of the promising potential of computational approaches to discover new anti-mycotoxin solutions Full article

(This article belongs to the Special Issue Computational Strategy for Drug Design)

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15 pages, 7120 KiB

Open AccessArticle

Thermodynamic Signatures of Structural Transitions and Dissociation of Charged Colloidal Clusters: A Parallel Tempering Monte Carlo Study

by Frederico V. Prudente and Jorge M. C. Marques

Molecules 2022, 27(8), 2581; https://doi.org/10.3390/molecules27082581 - 16 Apr 2022

Cited by 2 | Viewed by 1872

Abstract

Computational simulation of colloidal systems make use of empirical interaction potentials that are founded in well-established theory. In this work, we have performed parallel tempering Monte Carlo (PTMC) simulations to calculate heat capacity and to assess structural transitions, which may occur in charged [...] Read more.

Computational simulation of colloidal systems make use of empirical interaction potentials that are founded in well-established theory. In this work, we have performed parallel tempering Monte Carlo (PTMC) simulations to calculate heat capacity and to assess structural transitions, which may occur in charged colloidal clusters whose effective interactions are described by a sum of pair potentials with attractive short-range and repulsive long-range components. Previous studies on these systems have shown that the global minimum structure varies from spherical-type shapes for small-size clusters to Bernal spiral and “beaded-necklace” shapes at intermediate and larger sizes, respectively. In order to study both structural transitions and dissociation, we have organized the structures appearing in the PTMC calculations by three sets according to their energy: (i) low-energy structures, including the global minimum; (ii) intermediate-energy “beaded-necklace” motifs; (iii) high-energy linear and branched structures that characterize the dissociative clusters. We observe that, depending on the cluster, either peaks or shoulders on the heat–capacity curve constitute thermodynamics signatures of dissociation and structural transitions. The dissociation occurs at

T = 0.20

for all studied clusters and it is characterized by the appearance of a significant number of linear structures, while the structural transitions corresponding to unrolling the Bernal spiral are quite dependent on the size of the colloidal system. Full article

(This article belongs to the Special Issue Intermolecular Forces: From Atoms and Molecules to Nanostructures)

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15 pages, 1963 KiB

Open AccessArticle

Development and Application of an LC-MS/MS Untargeted Exposomics Method with a Separated Pooled Quality Control Strategy

by Gianfranco Frigerio, Camilla Moruzzi, Rosa Mercadante, Emma L. Schymanski and Silvia Fustinoni

Molecules 2022, 27(8), 2580; https://doi.org/10.3390/molecules27082580 - 16 Apr 2022

Cited by 6 | Viewed by 3475

Abstract

Pooled quality controls (QCs) are usually implemented within untargeted methods to improve the quality of datasets by removing features either not detected or not reproducible. However, this approach can be limiting in exposomics studies conducted on groups of exposed and nonexposed subjects, as [...] Read more.

Pooled quality controls (QCs) are usually implemented within untargeted methods to improve the quality of datasets by removing features either not detected or not reproducible. However, this approach can be limiting in exposomics studies conducted on groups of exposed and nonexposed subjects, as compounds present at low levels only in exposed subjects can be diluted and thus not detected in the pooled QC. The aim of this work is to develop and apply an untargeted workflow for human biomonitoring in urine samples, implementing a novel separated approach for preparing pooled quality controls. An LC-MS/MS workflow was developed and applied to a case study of smoking and non-smoking subjects. Three different pooled quality controls were prepared: mixing an aliquot from every sample (QC-T), only from non-smokers (QC-NS), and only from smokers (QC-S). The feature tables were filtered using QC-T (T-feature list), QC-S, and QC-NS, separately. The last two feature lists were merged (SNS-feature list). A higher number of features was obtained with the SNS-feature list than the T-feature list, resulting in identification of a higher number of biologically significant compounds. The separated pooled QC strategy implemented can improve the nontargeted human biomonitoring for groups of exposed and nonexposed subjects. Full article

(This article belongs to the Special Issue Mass Spectrometry in the Health Sciences)

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16 pages, 2526 KiB

Open AccessArticle

Compositional Analysis of Four Kinds of Citrus Fruits with an NMR-Based Method for Understanding Nutritional Value and Rational Utilization: From Pericarp to Juice

by Yong Pei, Chenxi He, Huili Liu, Guiping Shen and Jianghua Feng

Molecules 2022, 27(8), 2579; https://doi.org/10.3390/molecules27082579 - 16 Apr 2022

Cited by 15 | Viewed by 3231

Abstract

Citrus is one of the most important economic crops and is widely distributed across the monsoon region. Citrus fruits are deeply loved by consumers because of their special color, fragrance and high nutritional value. However, their health benefits have not been fully understood, [...] Read more.

Citrus is one of the most important economic crops and is widely distributed across the monsoon region. Citrus fruits are deeply loved by consumers because of their special color, fragrance and high nutritional value. However, their health benefits have not been fully understood, especially the pericarps of citrus fruits which have barely been utilized due to their unknown chemical composition. In the present study, the pericarp and juices of four typical varieties of citrus fruits (lemon, dekopon, sweet orange and pomelo) were analyzed by NMR spectroscopy combined with pattern recognition. A total of 62 components from the citrus juices and 87 components from the citrus pericarps were identified and quantified, respectively. The different varieties of the citrus fruits could be distinguished from the others, and the chemical markers in each citrus juice and pericarp were identified by a combination of univariate and multivariate statistical analyses. The nutritional analysis of citrus juices offers favorable diet recommendations for human consumption and data guidance for their potential medical use, and the nutritional analysis of citrus pericarps provides a data reference for the subsequent comprehensive utilization of citrus fruits. Our results not only provide an important reference for the potential nutritional and medical values of citrus fruits but also provide a feasible platform for the traceability analysis, adulteration identification and chemical composition analysis of other fruits. Full article

(This article belongs to the Special Issue NMR-Based Metabolomics and Human Health)

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12 pages, 679 KiB

Open AccessArticle

Anti-Staphylococcal Activity of the Auranofin Analogue Bearing Acetylcysteine in Place of the Thiosugar: An Experimental and Theoretical Investigation

by Lorenzo Chiaverini, Alessandro Pratesi, Damiano Cirri, Arianna Nardinocchi, Iogann Tolbatov, Alessandro Marrone, Mariagrazia Di Luca, Tiziano Marzo and Diego La Mendola

Molecules 2022, 27(8), 2578; https://doi.org/10.3390/molecules27082578 - 16 Apr 2022

Cited by 7 | Viewed by 2291

Abstract

Auranofin (AF, hereafter) is an orally administered chrysotherapeutic agent approved for the treatment of rheumatoid arthritis that is being repurposed for various indications including bacterial infections. Its likely mode of action involves the impairment of the TrxR system through the binding of the [...] Read more.

Auranofin (AF, hereafter) is an orally administered chrysotherapeutic agent approved for the treatment of rheumatoid arthritis that is being repurposed for various indications including bacterial infections. Its likely mode of action involves the impairment of the TrxR system through the binding of the pharmacophoric cation [AuPEt₃]⁺. Accordingly, a reliable strategy to expand the medicinal profile of AF is the replacement of the thiosugar moiety with different ligands. Herein, we aimed to prepare the AF analogue bearing the acetylcysteine ligand (AF-AcCys, hereafter) and characterize its anti-staphylococcal activity. Biological studies revealed that AF-AcCys retains an antibacterial effect superimposable with that of AF against Staphylococcus aureus, whereas it is about 20 times less effective against Staphylococcus epidermidis. Bioinorganic studies confirmed that upon incubation with human serum albumin, AF-AcCys, similarly to AF, induced protein metalation through the [AuPEt₃]⁺ fragment. Additionally, AF-AcCys appeared capable of binding the dodecapeptide Ac-SGGDILQSGCUG-NH₂, corresponding to the tryptic C-terminal fragment (488–499) of hTrxR. To shed light on the pharmacological differences between AF and AF-AcCys, we carried out a comparative experimental stability study and a theoretical estimation of bond dissociation energies, unveiling the higher strength of the Au–S bond in AF-AcCys. From the results, it emerged that the lower lipophilicity of AF-AcCys with respect to AF could be a key feature for its different antibacterial activity. The differences and similarities between AF and AF-AcCys are discussed, alongside the opportunities and consequences that chemical structure modifications imply. Full article

(This article belongs to the Special Issue Inorganic Compounds in Medicine, Cancer Therapy and Beyond – an Update from Drug Design Perspective)

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