Molecules

22 pages, 2912 KiB

Open AccessArticle

New Thiazolyl-Pyrazoline Derivatives as Potential Dual EGFR/HER2 Inhibitors: Design, Synthesis, Anticancer Activity Evaluation and In Silico Study

by Mariam M. Fakhry, Amr A. Mattar, Marwa Alsulaimany, Ebtesam M. Al-Olayan, Sara T. Al-Rashood and Hatem A. Abdel-Aziz

Molecules 2023, 28(21), 7455; https://doi.org/10.3390/molecules28217455 - 6 Nov 2023

Cited by 9 | Viewed by 1940

Abstract

A new series of thiazolyl-pyrazoline derivatives (4a–d, 5a–d 6a, b, 7a–d, 8a, b, and 10a, b) have been designed and synthesized through the combination of thiazole and pyrazoline [...] Read more.

A new series of thiazolyl-pyrazoline derivatives (4a–d, 5a–d 6a, b, 7a–d, 8a, b, and 10a, b) have been designed and synthesized through the combination of thiazole and pyrazoline moieties, starting from the key building blocks pyrazoline carbothioamides (1a–b). These eighteen derivatives have been designed as anticipated EGFR/HER2 dual inhibitors. The efficacy of the developed compounds in inhibiting cell proliferation was assessed using the breast cancer MCF-7 cell line. Among the new synthesized thiazolyl-pyrazolines, compounds 6a, 6b, 10a, and 10b displayed potent anticancer activity toward MCF-7 with IC₅₀ = 4.08, 5.64, 3.37, and 3.54 µM, respectively, when compared with lapatinib (IC₅₀ = 5.88 µM). In addition, enzymatic assays were also run for the most cytotoxic compounds (6a and 6b) toward EGFR and HER2 to demonstrate their dual inhibitory activity. They revealed promising inhibition potency against EGFR with IC₅₀ = 0.024, and 0.005 µM, respectively, whereas their IC₅₀ = 0.047 and 0.022 µM toward HER2, respectively, compared with lapatinib (IC₅₀ = 0.007 and 0.018 µM). Both compounds 6a and 10a induced apoptosis by arresting the cell cycle of the MCF-7 cell line at the G1 and G1/S phases, respectively. Molecular modeling studies for the promising candidates 6a and 10a showed that they formed the essential binding with the crucial amino acids for EGFR and HER2 inhibition, supporting the in vitro assay results. Furthermore, ADMET study predictions were carried out for the compounds in the study. Full article

(This article belongs to the Special Issue Synthesis and Evaluation of Biologically Active Compounds from Five Membered Heterocycles)

► Show Figures

Graphical abstract

17 pages, 2380 KiB

Open AccessArticle

Possible Roles of Transition Metal Cations in the Formation of Interstellar Benzene via Catalytic Acetylene Cyclotrimerization

by Tatsuhiro Murakami, Naoki Matsumoto, Takashi Fujihara and Toshiyuki Takayanagi

Molecules 2023, 28(21), 7454; https://doi.org/10.3390/molecules28217454 - 6 Nov 2023

Cited by 2 | Viewed by 1712

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous interstellar molecules. However, the formation mechanisms of PAHs and even the simplest cyclic aromatic hydrocarbon, benzene, are not yet fully understood. Recently, we reported the statistical and dynamical properties in the reaction mechanism of Fe⁺-catalyzed [...] Read more.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous interstellar molecules. However, the formation mechanisms of PAHs and even the simplest cyclic aromatic hydrocarbon, benzene, are not yet fully understood. Recently, we reported the statistical and dynamical properties in the reaction mechanism of Fe⁺-catalyzed acetylene cyclotrimerization, whereby three acetylene molecules are directly converted to benzene. In this study, we extended our previous work and explored the possible role of the complex of other 3d transition metal cations, TM⁺ (TM = Sc, Ti, Mn, Co, and Ni), as a catalyst in acetylene cyclotrimerization. Potential energy profiles for bare TM⁺-catalyst (TM = Sc and Ti), for TM⁺NC⁻-catalyst (TM = Sc, Ti, Mn, Co, and Ni), and for TM⁺-(H₂O)₈-catalyst (TM = Sc and Ti) systems were obtained using quantum chemistry calculations, including the density functional theory levels. The calculation results show that the scandium and titanium cations act as efficient catalysts in acetylene cyclotrimerization and that reactants, which contain an isolated acetylene and (C₂H₂)₂ bound to a bare (ligated) TM cation (TM = Sc and Ti), can be converted into a benzene–metal–cation product complex without an entrance barrier. We found that the number of electrons in the 3d orbitals of the transition metal cation significantly contributes to the catalytic efficiency in the acetylene cyclotrimerization process. On-the-fly Born–Oppenheimer molecular dynamics (BOMD) simulations of the Ti⁺-NC⁻ and Ti⁺-(H₂O)₈ complexes were also performed to comprehensively understand the nuclear dynamics of the reactions. The computational results suggest that interstellar benzene can be produced via acetylene cyclotrimerization reactions catalyzed by transition metal cation complexes. Full article

(This article belongs to the Topic Theoretical, Quantum and Computational Chemistry)

► Show Figures

Graphical abstract

14 pages, 1573 KiB

Open AccessArticle

Antimicrobial Activity of Manganese(I) Tricarbonyl Complexes Bearing 1,2,3-Triazole Ligands

by Sofia Friães, Cândida Trigueiros, Clara S. B. Gomes, Alexandra R. Fernandes, Oscar A. Lenis-Rojas, Marta Martins and Beatriz Royo

Molecules 2023, 28(21), 7453; https://doi.org/10.3390/molecules28217453 - 6 Nov 2023

Cited by 2 | Viewed by 2105

Abstract

Background. Antimicrobial resistance is one of the most pressing health issues of our time. The increase in the number of antibiotic-resistant bacteria allied to the lack of new antibiotics has contributed to the current crisis. It has been predicted that if this situation [...] Read more.

Background. Antimicrobial resistance is one of the most pressing health issues of our time. The increase in the number of antibiotic-resistant bacteria allied to the lack of new antibiotics has contributed to the current crisis. It has been predicted that if this situation is not dealt with, we will be facing 10 million deaths due to multidrug resistant infections per year by 2050, surpassing cancer-related deaths. This alarming scenario has refocused attention into researching alternative drugs to treat multidrug-resistant infections. Aims. In this study, the antimicrobial activities of four manganese complexes containing 1,2,3,-triazole and clotrimazole ligands have been evaluated. It is known that azole antibiotics coordinated to manganese tricarbonyl complexes display interesting antimicrobial activities against several microbes. In this work, the effect of the introduction of 1,2,3,-triazole-derived ligands in the [Mn(CO)₃(clotrimazole)] fragment has been investigated against one Gram-positive bacterium and five Gram-negative bacteria. Methods. The initial antimicrobial activity of the above-mentioned complexes was assessed by determining the minimum inhibitory and bactericidal concentrations using the broth microdilution method. Growth curves in the presence and absence of the complexes were performed to determine the effects of these complexes on the growth of the selected bacteria. A possible impact on cellular viability was determined by conducting the MTS assay on human monocytes. Results. Three of the Mn complexes investigated (4–6) had good antimicrobial activities against all the bacteria tested, with values ranging from 1.79 to 61.95 µM with minimal toxicity. Conclusions. Due to the increased problem of antibiotic resistance and a lack of new antibacterial drugs with no toxicity, these results are exciting and show that these types of complexes can be an avenue to pursue in the future. Full article

(This article belongs to the Special Issue Exclusive Feature Papers in Inorganic Chemistry, 2nd Edition)

► Show Figures

Graphical abstract

15 pages, 6995 KiB

Open AccessArticle

Three-Dimensional Porous PVDF Foam Imprinted Membranes with High Flux and Selectivity toward Artemisinin/Artemether

by Weibai Bian, Ruixuan Zhang, Xiaohui Chen, Chuanxun Zhang and Minjia Meng

Molecules 2023, 28(21), 7452; https://doi.org/10.3390/molecules28217452 - 6 Nov 2023

Cited by 2 | Viewed by 1256

Abstract

In this study, a new 3D porous PVDF-foam-imprinted membrane (PPIM) for the selective separation of artemisinin (ART) was first prepared via the dopamine adhesion of pre-synthesized MIPs into the interior of the PPIM. In the PPIM, the pre-synthesized molecularly imprinted polymers (MIPs) with [...] Read more.

In this study, a new 3D porous PVDF-foam-imprinted membrane (PPIM) for the selective separation of artemisinin (ART) was first prepared via the dopamine adhesion of pre-synthesized MIPs into the interior of the PPIM. In the PPIM, the pre-synthesized molecularly imprinted polymers (MIPs) with artesunate (ARU) as a dummy template were uniformly loaded on the interior of the membrane, avoiding the defects of recognition site encapsulation found in the conventional membrane. This membrane also exhibited excellent flux, which is beneficial in practical separation applications. The PPIM was systematically characterized via FT-IR, SEM, pore-size distribution analysis, water contact angle test, membrane flux, and mechanical performance analysis, respectively. In the static adsorption experiment, the pseudo-second-order kinetic model better fitted the rebinding data of ART. Under dynamic conditions, the ART adsorption capacity of the PPIM could be further remarkably improved by tailoring the flow rate to 3 mL min⁻¹. In the selective separation experiment, with artemether (ARE) as the competition substrate, the selective separation ability (α) of the PPIM towards ART/artemether (ARE) reached its peak value (3.16) within only 10 min at this flow rate, which is higher than that of porous PVDF foam non-imprinted membranes (PPNM) (ca. 1.5), showing great separation efficiency in a short time. Moreover, the PPIM can be reused five times without a significant decrease in its adsorption capacities, showing good regeneration performance. This work highlights a simple strategy for constructing new MIMs with high flux and great mechanical strength to achieve the efficient selective separation of ART and ARE in practical applications. Full article

(This article belongs to the Special Issue Exclusive Papers Collection of Editorial Board Members and Invited Scholars in Applied Chemistry)

► Show Figures

Graphical abstract

19 pages, 2921 KiB

Open AccessArticle

Identification of the Metabolites of Both Formononetin in Rat Hepatic S9 and Ononin in Rat Urine Samples and Preliminary Network Pharmacology Evaluation of Their Main Metabolites

by Yu-Zhu Yang, Tao Wang, Qi-Lei Chen, Hu-Biao Chen, Qian-Song He and Ya-Zhou Zhang

Molecules 2023, 28(21), 7451; https://doi.org/10.3390/molecules28217451 - 6 Nov 2023

Cited by 2 | Viewed by 1688

Abstract

Astragalus membranaceus is a traditional Chinese medicine derived from the roots of Astragalus membranaceus (Fisch.) Bge., which has the same medicinal and edible uses in China. It is also widely used in daily food, and its pharmacological effects mainly include antioxidant effects, vascular [...] Read more.

Astragalus membranaceus is a traditional Chinese medicine derived from the roots of Astragalus membranaceus (Fisch.) Bge., which has the same medicinal and edible uses in China. It is also widely used in daily food, and its pharmacological effects mainly include antioxidant effects, vascular softening effects, etc. Currently, it is increasingly widely used in the prevention of hypertension, cerebral ischemia, and stroke in China. Formononetin and its glucopyranoside (ononin) are both important components of Astragalus membranaceuss and may play important roles in the treatment of cardiovascular diseases (CVDs). This study conducted metabolic studies using formononectin and its glucopyranoside (ononin), including a combination of the in vitro metabolism of Formonetin using rat liver S9 and the in vivo metabolism of ononin administered orally to rats. Five metabolites (Sm2, 7, 9, 10, and 12) were obtained from the solution incubated with formononetin and rat hepatic S9 fraction using chromatographic methods. The structures of the five metabolites were elucidated as (Sm2)6,7,4′-trihydroxy-isoflavonoid; (Sm7)7,4′-dihydroxy-isoflavonoid; (Sm9)7,8,4′-trihydroxy-isoflavonoid; (Sm10)7,8,-dihydroxy-4′-methoxy-isoflavonoid; and (Sm12)6,7-dihydroxy-4′-methoxy- isoflavonoid on the basis of UV, NMR, and MS data. Totally, 14 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSⁿ analysis, from which the formononetin was incubated with rat hepatic S9 fraction, and the main metabolic pathways were hydroxylation, demethylation, and glycosylation. Then, 21 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSⁿ analysis from the urine samples from SD rats to which ononin was orally administered, and the main metabolic pathways were glucuronidation, hydroxylation, demethylation, and sulfonation. The main difference between the in vitro metabolism of formononetin and the in vivo metabolism of ononin is that ononin undergoes deglycemic transformation into Formonetin in the rat intestine, while Formonetin is absorbed into the bloodstream for metabolism, and the metabolic products also produce combined metabolites during in vivo metabolism. The six metabolites obtained from the aforementioned separation indicate the primary forms of formononetin metabolism, and due to their higher contents of similar isoflavone metabolites, they are considered the main active compounds that are responsible for pharmacological effects. To investigate the metabolites of the active ingredients of formononetin in the rat liver S9 system, network pharmacology was used to evaluate the cardiovascular disease (CVD) activities of the six primary metabolites that were structurally identified. Additionally, the macromolecular docking results of six main components and two core targets (HSP90AA1 and SRC) related to CVD showed that formononetin and its main metabolites, Sm10 and Sm12, may have roles in CVD treatment due to their strong binding activities with the HSP90AA1 receptor, while the Sm7 metabolite may have a role in CVD treatment due to its strong binding activity with the SRC receptor. Full article

(This article belongs to the Special Issue Therapeutic and Nutraceutical Values of Functional Foods or Compounds)

► Show Figures

Figure 1

12 pages, 1301 KiB

Open AccessArticle

Base-Catalyzed Nucleophilic Addition Reaction of Indoles with Vinylene Carbonate: An Approach to Synthesize 4-Indolyl-1,3-dioxolanones

by Xia Chen, Xiao-Yu Zhou and Ming Bao

Molecules 2023, 28(21), 7450; https://doi.org/10.3390/molecules28217450 - 6 Nov 2023

Cited by 2 | Viewed by 1407

Abstract

The N-functionalized indole is a privileged structural framework in a wide range of bioactive molecules. The nucleophilic addition between indoles with vinylene carbonate proceeded smoothly in the presence of K₂CO₃ as the catalyst to produce novel indolyl-containing skeletons and [...] Read more.

The N-functionalized indole is a privileged structural framework in a wide range of bioactive molecules. The nucleophilic addition between indoles with vinylene carbonate proceeded smoothly in the presence of K₂CO₃ as the catalyst to produce novel indolyl-containing skeletons and 4-indolyl-1,3-dioxolanones in satisfactory to excellent yields (up to >97% yield). Various synthetically useful functional groups, such as halogen atoms, cyano, nitro, and methoxycarbonyl groups, remained intact during the regioselective N-H addition reactions. The developed catalytic system also could accommodate 2-naphthalenol to achieve the target O-H additive product in good yield. Full article

(This article belongs to the Special Issue The Design and Synthesis of Indole Derivatives and Their Metal Complexes)

► Show Figures

Figure 1

23 pages, 22985 KiB

Open AccessArticle

Effects of Radiation-Induced Skin Injury on Hyaluronan Degradation and Its Underlying Mechanisms

by Jiahui Dong, Boyuan Ren, Yunfei Tian, Guanqun Peng, Huiting Zhai, Zhiyun Meng, Ruolan Gu, Hui Gan, Zhuona Wu, Yunbo Sun, Guifang Dou and Shuchen Liu

Molecules 2023, 28(21), 7449; https://doi.org/10.3390/molecules28217449 - 6 Nov 2023

Cited by 1 | Viewed by 1847

Abstract

Radiation-induced skin injury (RISI) is a frequent and severe complication with a complex pathogenesis that often occurs during radiation therapy, nuclear incidents, and nuclear war, for which there is no effective treatment. Hyaluronan (HA) plays an overwhelming role in the skin, and it [...] Read more.

Radiation-induced skin injury (RISI) is a frequent and severe complication with a complex pathogenesis that often occurs during radiation therapy, nuclear incidents, and nuclear war, for which there is no effective treatment. Hyaluronan (HA) plays an overwhelming role in the skin, and it has been shown that UVB irradiation induces increased HA expression. Nevertheless, to the best of our knowledge, there has been no study regarding the biological correlation between RISI and HA degradation and its underlying mechanisms. Therefore, in our study, we investigated low-molecular-weight HA content using an enzyme-linked immunosorbent assay and changes in the expression of HA-related metabolic enzymes using real-time quantitative polymerase chain reaction and a Western blotting assay. The oxidative stress level of the RISI model was assessed using sodium dismutase, malondialdehyde, and reactive oxygen species assays. We demonstrated that low-molecular-weight HA content was significantly upregulated in skin tissues during the late phase of irradiation exposure in the RISI model and that HA-related metabolic enzymes, oxidative stress levels, the MEK5/ERK5 pathway, and inflammatory factors were consistent with changes in low-molecular-weight HA content. These findings prove that HA degradation is biologically relevant to RISI development and that the HA degradation mechanisms are related to HA-related metabolic enzymes, oxidative stress, and inflammatory factors. The MEK5/ERK5 pathway represents a potential mechanism of HA degradation. In conclusion, we aimed to investigate changes in HA content and preliminarily investigate the HA degradation mechanism in a RISI model under γ-ray irradiation, to consider HA as a new target for RISI and provide ideas for novel drug development. Full article

► Show Figures

Figure 1

16 pages, 4476 KiB

Open AccessArticle

Structural Analysis and Antioxidant and Immunoregulatory Activities of an Exopolysaccharide Isolated from Bifidobacterium longum subsp. longum XZ01

by Xingyuan Zhang, Jing Gong, Wenyi Huang, Wen Liu, Chong Ma, Rongyao Liang, Ye Chen, Zhiyong Xie, Pei Li and Qiongfeng Liao

Molecules 2023, 28(21), 7448; https://doi.org/10.3390/molecules28217448 - 6 Nov 2023

Cited by 3 | Viewed by 1451

Abstract

Bifidobacterium longum subsp. longum XZ01 (BLSL1) is a new strain (isolated from the intestines of healthy people and deposited with the preservation number GDMCC 61618). An exopolysaccharide, S-EPS-1, was successfully isolated from the strain and then systematically investigated for the first time. Some [...] Read more.

Bifidobacterium longum subsp. longum XZ01 (BLSL1) is a new strain (isolated from the intestines of healthy people and deposited with the preservation number GDMCC 61618). An exopolysaccharide, S-EPS-1, was successfully isolated from the strain and then systematically investigated for the first time. Some structural features of S-EPS-1 were analyzed by chemical component, HPLC, ultraviolet, infrared, and nuclear magnetic resonance spectrum analyses. These analyses revealed that S-EPS-1 is a neutral heteropolysaccharide with an α-configuration. It contains mainly mannose and glucose, as well as small amounts of rhamnose and galactose. The molecular weight of S-EPS-1 was calculated to be 638 kDa. Several immunoregulatory activity assays indicated that S-EPS-1 could increase proliferation, phagocytosis, and NO production in vitro. In addition, S-EPS-1 could upregulate the expression of cytokines at the mRNA level through TLR4-mediated activation of the NF-κB signaling pathway in RAW 264.7 cells. Finally, S-EPS-1 was demonstrated to exhibit antioxidant activity by ABTS^+• scavenging, DPPH^• scavenging, and ferric-ion reducing power assays. Furthermore, S-EPS-1 can protect cells from oxidative stress and shows no cytotoxicity. These beneficial effects can be partly attributed to its antioxidant ability. Thus, the antioxidant S-EPS-1 may be applied as a functional food in the future. Full article

(This article belongs to the Special Issue Antioxidants in Herbal Medicine and Natural Products)

► Show Figures

Graphical abstract

15 pages, 10169 KiB

Open AccessArticle

Study on the Dynamic Changes in Non-Volatile Metabolites of Rizhao Green Tea Based on Metabolomics

by Ao Sun, Guolong Liu, Luyan Sun, Chun Li, Qiu Wu, Jianhua Gao, Yuanzhi Xia and Yue Geng

Molecules 2023, 28(21), 7447; https://doi.org/10.3390/molecules28217447 - 6 Nov 2023

Cited by 1 | Viewed by 1841

Abstract

The processing of tea leaves plays a crucial role in the formation of the taste of the resulting tea. In order to study the compositions of and changes in taste-related substances during the processing of Rizhao green tea, non-targeted metabolomics was used, based [...] Read more.

The processing of tea leaves plays a crucial role in the formation of the taste of the resulting tea. In order to study the compositions of and changes in taste-related substances during the processing of Rizhao green tea, non-targeted metabolomics was used, based on UHPLC-Q Exactive MS. Totals of 529, 349, and 206 non-volatile metabolites were identified using three different detection modes, of which 112 secondary metabolites were significantly changed. Significant variations in secondary metabolites were observed during processing, especially during the drying stage, and the conversion intensity levels of non-volatile metabolites were consistent with the law of “Drying > Fixation > Rolling”. The DOT method was used to screen tea-quality-related compounds that contributed significantly to the taste of Rizhao green tea, including (−)-epicatechin gallate, (−)-epicatechin gallate, gallic acid, L-theanine, and L-leucine, which make important contributions to taste profiles, such as umami and bitterness. Metabolic pathway analysis revealed that purine metabolism, caffeine metabolism, and tyrosine metabolism perform key roles in the processing of Rizhao green tea in different processing stages. The results of this study provide a theoretical basis for tea processing and practical advice for the food industry. Full article

(This article belongs to the Section Flavours and Fragrances)

► Show Figures

Graphical abstract

13 pages, 4891 KiB

Open AccessArticle

New Tricholomalides D–G from the Mushroom Tricholoma ustaloides Grown in an Italian Beech Wood

by Gianluca Gilardoni, Francesca Negri, Paola Vita Finzi, Faiq H. S. Hussain and Giovanni Vidari

Molecules 2023, 28(21), 7446; https://doi.org/10.3390/molecules28217446 - 6 Nov 2023

Cited by 1 | Viewed by 1154

Abstract

Four novel seconeodolastane diterpenoids, named tricholomalides D–G, were isolated, together with the known tricholomalide C, from the fruiting bodies of Tricholoma ustaloides Romagn., a species belonging to the large Tricholoma genus of higher mushrooms (Basidiomycota, family Tricholomataceae). They were isolated [...] Read more.

Four novel seconeodolastane diterpenoids, named tricholomalides D–G, were isolated, together with the known tricholomalide C, from the fruiting bodies of Tricholoma ustaloides Romagn., a species belonging to the large Tricholoma genus of higher mushrooms (Basidiomycota, family Tricholomataceae). They were isolated through multiple chromatographic separations, and the structures, including the absolute configuration, were established through a detailed analysis of MS, NMR, and CD spectral data and comparison with related compounds reported in the literature, which has been thoroughly revised. Full article

(This article belongs to the Special Issue Terpenoid Natural Products: Discovery, Biological Evaluation, and Structural Modification)

► Show Figures

Figure 1

12 pages, 3577 KiB

Open AccessArticle

Effects of the Supercritical Fluid Extract of Magnolia figo on Inducing the Apoptosis of Human Non-Small-Cell Lung Cancer Cells

by Chun-Sheng Kuo, Shih-Yun Chen and Jen-Chieh Tsai

Molecules 2023, 28(21), 7445; https://doi.org/10.3390/molecules28217445 - 6 Nov 2023

Viewed by 1761

Abstract

Lung cancer has a high incidence rate worldwide, necessitating the development of new drugs. Although Magnolia figo (Lour.) DC. is known for its medicinal properties, studies on its efficacy against lung cancer are lacking. This study investigated whether the supercritical fluid extract of [...] Read more.

Lung cancer has a high incidence rate worldwide, necessitating the development of new drugs. Although Magnolia figo (Lour.) DC. is known for its medicinal properties, studies on its efficacy against lung cancer are lacking. This study investigated whether the supercritical fluid extract of M. figo (FMO) can induce apoptosis in A549, a human non-small-cell lung cancer cell line. The cell viability was assessed using an MTT assay. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis and flow cytometry analysis were conducted. The expression of factors was assessed through Western blotting analyses. Gas chromatography–mass spectrometry (GC-MS) was performed. The results revealed that FMO treatment exhibited cytotoxicity, demonstrating dose-dependent effects. The TUNEL analysis and flow cytometry analysis revealed that FMO induced apoptosis in A549 cells. The Western blotting analysis revealed that FMO upregulated the expression of p53 and Bax protein, and downregulated the expression of Bcl-2 protein. The GC-MS analysis revealed eight components identified in FMO. These findings indicate that FMO can induce A549 apoptosis through the p53/Bcl-2/Bax pathways, confirming the apoptotic effects of M. figo on lung cancer cells. These results highlight the potential, for the first time, of M. figo as a source for developing novel drugs for lung cancer treatment. Full article

► Show Figures

Graphical abstract

27 pages, 773 KiB

Open AccessReview

Mentha piperita: Essential Oil and Extracts, Their Biological Activities, and Perspectives on the Development of New Medicinal and Cosmetic Products

by Nataliia Hudz, Lesya Kobylinska, Katarzyna Pokajewicz, Vladimira Horčinová Sedláčková, Roman Fedin, Mariia Voloshyn, Iryna Myskiv, Ján Brindza, Piotr Paweł Wieczorek and Jacek Lipok

Molecules 2023, 28(21), 7444; https://doi.org/10.3390/molecules28217444 - 6 Nov 2023

Cited by 18 | Viewed by 8488

Abstract

This review aims to analyze Mentha piperita L. as a potential raw material for the development of new health-promoting products (nutraceuticals, cosmetics, and pharmaceutical products). A lot of scientific publications were retrieved from the Scopus, PubMed, and Google Scholar databases which enable the [...] Read more.

This review aims to analyze Mentha piperita L. as a potential raw material for the development of new health-promoting products (nutraceuticals, cosmetics, and pharmaceutical products). A lot of scientific publications were retrieved from the Scopus, PubMed, and Google Scholar databases which enable the study and generalization of the extraction procedures, key biologically active compounds of essential oil and extracts, biological properties, and therapeutic potential of M. piperita, along with perspectives on the development of its dosage forms, including combinations of synthetic active substances and herbal preparations of M. piperita. The results of this review indicate that M. piperita is a source rich in phytoconstituents of different chemical nature and can be regarded as a source of active substances to enhance health and to develop medicinal products for complementary therapy of various conditions, especially those related with oxidant stress, inflammation, and moderate infections. Essential oil has a broad spectrum of activities. Depending on the test and concentration, this essential oil has both anti- and prooxidant properties. Gram-positive bacteria are more sensitive to the essential oil of M. piperita than Gram-negative ones. This review also considered some facets of the standardization of essential oil and extracts of M. piperita. Among the identified phenolics of extracts were caffeic acid, rosmarinic acid, eriocitrin, luteolin derivates (luteolin-7-O-rutinoside, luteolin-7-O-glucoronide), and hesperidin. The concentration of these phenolics depends on the solvent used. This review also considered the relationships between the chemical component and biological activity. The results showed that the essential oil and extracts reduced inflammation in vitro by inhibiting the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and in vivo by reducing the paw edema induced using carrageenan injection in rats. Therefore, herbal preparations of M. piperita are promising medicinal and cosmetic preparations for their usage in skincare and oral cavity care products with antimicrobial, anti-inflammatory, and wound-healing properties. This plant can also be regarded as a platform for the development of antibacterial preparations and combined anti-inflammatory and cardioprotective medicinal products (synthetic active substances plus herbal preparations). This review could be considered for the justification of the composition of some medicinal products during their pharmaceutical development for writing a registration dossier in the format of Common Technical Document. Full article

(This article belongs to the Special Issue Essential Oils: From Extraction to Application)

► Show Figures

Graphical abstract

27 pages, 5513 KiB

Open AccessArticle

Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities

by Amani Toumi, Faiza I.A. Abdella, Sarra Boudriga, Tahani Y. A. Alanazi, Asma K. Alshamari, Ahlam Abdulrahman Alrashdi, Amal Dbeibia, Khaled Hamden, Ismail Daoud, Michael Knorr, Jan-Lukas Kirchhoff and Carsten Strohmann

Molecules 2023, 28(21), 7443; https://doi.org/10.3390/molecules28217443 - 6 Nov 2023

Cited by 4 | Viewed by 2120

Abstract

In a sustained search for novel potential drug candidates with multispectrum therapeutic application, a series of novel spirooxindoles was designed and synthesized via regioselective three-component reaction between isatin derivatives, 2-phenylglycine and diverse arylidene-imidazolidine-2,4-diones (Hydantoins). The suggested stereochemistry was ascertained by an X-ray diffraction [...] Read more.

In a sustained search for novel potential drug candidates with multispectrum therapeutic application, a series of novel spirooxindoles was designed and synthesized via regioselective three-component reaction between isatin derivatives, 2-phenylglycine and diverse arylidene-imidazolidine-2,4-diones (Hydantoins). The suggested stereochemistry was ascertained by an X-ray diffraction study and NMR spectroscopy. The resulting tetracyclic heterocycles were screened for their in vitro and in vivo anti-inflammatory and analgesic activity and for their in vitro antimicrobial potency. In vitro antibacterial screening revealed that several derivatives exhibited remarkable growth inhibition against different targeted microorganisms. All tested compounds showed excellent activity against the Micrococccus luteus strain (93.75 µg/mL ≤ MIC ≤ 375 µg/mL) as compared to the reference drug tetracycline (MIC = 500 µg/mL). Compound 4e bearing a p-chlorophenyl group on the pyrrolidine ring exhibited the greatest antifungal potential toward Candida albicans and Candida krusei (MIC values of 23.43 µg/mL and 46.87 µg/mL, respectively) as compared to Amphotericin B (MIC = 31.25 and 62.50 µg/mL, respectively). The target compounds were also tested in vitro against the lipoxygenase-5 (LOX-5) enzyme. Compounds 4i and 4l showed significant inhibitory activity with IC₅₀ = 1.09 mg/mL and IC₅₀ = 1.01 mg/mL, respectively, more potent than the parent drug, diclofenac sodium (IC₅₀ = 1.19 mg/mL). In addition, in vivo evaluation of anti-inflammatory and analgesic activity of these spirooxindoles were assessed through carrageenan-induced paw edema and acetic acid-induced writhing assays, respectively, revealing promising results. In silico molecular docking and predictive ADMET studies for the more active spirocompounds were also carried out. Full article

(This article belongs to the Special Issue Novel Insights toward the Development of New Drugs)

► Show Figures

Figure 1

15 pages, 1222 KiB

Open AccessArticle

Total Synthesis of Nicrophorusamide A and Structural Disproof of the Proposed Noursamycin A

by Xiaoyun Liao, Shupeng Li, Yian Guo and Tao Ye

Molecules 2023, 28(21), 7442; https://doi.org/10.3390/molecules28217442 - 6 Nov 2023

Cited by 1 | Viewed by 1472

Abstract

Total synthesis of the proposed noursamycin A has been accomplished, which disproves the original structural assignments. The synthetic strategy described herein has also been employed in the first total synthesis of nicrophorusamide A, a cyclopeptide that is structurally related to noursamycin A. Full article

(This article belongs to the Special Issue The Design, Synthesis, and Biological Activity of New Drug Candidates)

► Show Figures

Scheme 1

14 pages, 5408 KiB

Open AccessArticle

Exploring the Impact of Intermolecular Interactions on the Glassy Phase Formation of Twist-Bend Liquid Crystal Dimers: Insights from Dielectric Studies

by Antoni Kocot, Małgorzata Czarnecka, Yuki Arakawa and Katarzyna Merkel

Molecules 2023, 28(21), 7441; https://doi.org/10.3390/molecules28217441 - 6 Nov 2023

Viewed by 1243

Abstract

The formation of the nematic to twist-bend nematic (N_TB) phase has emerged as a fascinating phenomenon in the field of supramolecular chemistry, based on complex intermolecular interactions. Through a careful analysis of molecular structures and dynamics, we elucidate how these intermolecular [...] Read more.

The formation of the nematic to twist-bend nematic (N_TB) phase has emerged as a fascinating phenomenon in the field of supramolecular chemistry, based on complex intermolecular interactions. Through a careful analysis of molecular structures and dynamics, we elucidate how these intermolecular interactions drive the complex twist-bend modulation observed in the N_TB. The study employs broadband dielectric spectroscopy spanning frequencies from 10 to 2 × 10⁹ Hz to investigate the molecular orientational dynamics within the glass-forming thioether-linked cyanobiphenyl liquid crystal dimers, namely, CBSC7SCB and CBSC7OCB. The experimental findings align with theoretical expectations, revealing the presence of two distinct relaxation processes contributing to the dielectric permittivity of these dimers. The low-frequency relaxation mode is attributed to an “end-over-end rotation” of the dipolar groups parallel to the director. The high-frequency relaxation mode is associated with precessional motions of the dipolar groups about the director. Various models are employed to describe the temperature-dependent behavior of the relaxation times for both modes. Particularly, the critical-like description via the dynamic scaling model seems to give not only quite good numerical fittings, but also provides a consistent physical picture of the orientational dynamics in accordance with findings from infrared (IR) spectroscopy. Here, as the longitudinal correlations of dipoles intensify, the m₁ mode experiences a sudden upsurge in enthalpy, while the m₂ mode undergoes continuous changes, displaying critical mode coupling behavior. Interestingly, both types of molecular motion exhibit a strong cooperative interplay within the lower temperature range of the N_TB phase, evolving in tandem as the material’s temperature approaches the glass transition point. Consequently, both molecular motions converge to determine the glassy dynamics, characterized by a shared glass transition temperature, T_g. Full article

(This article belongs to the Special Issue Liquid Crystals II)

► Show Figures

Graphical abstract

59 pages, 14980 KiB

Open AccessReview

Natural Products–Pyrazine Hybrids: A Review of Developments in Medicinal Chemistry

by Guo-Qing Chen, Hong-Yan Guo, Zhe-Shan Quan, Qing-Kun Shen, Xiaoting Li and Tian Luan

Molecules 2023, 28(21), 7440; https://doi.org/10.3390/molecules28217440 - 5 Nov 2023

Cited by 6 | Viewed by 2655

Abstract

Pyrazine is a six-membered heterocyclic ring containing nitrogen, and many of its derivatives are biologically active compounds. References have been downloaded through Web of Science, PubMed, Science Direct, and SciFinder Scholar. The structure, biological activity, and mechanism of natural product derivatives containing pyrazine [...] Read more.

Pyrazine is a six-membered heterocyclic ring containing nitrogen, and many of its derivatives are biologically active compounds. References have been downloaded through Web of Science, PubMed, Science Direct, and SciFinder Scholar. The structure, biological activity, and mechanism of natural product derivatives containing pyrazine fragments reported from 2000 to September 2023 were reviewed. Publications reporting only the chemistry of pyrazine derivatives are beyond the scope of this review and have not been included. The results of research work show that pyrazine-modified natural product derivatives have a wide range of biological activities, including anti-inflammatory, anticancer, antibacterial, antiparasitic, and antioxidant activities. Many of these derivatives exhibit stronger pharmacodynamic activity and less toxicity than their parent compounds. This review has a certain reference value for the development of heterocyclic compounds, especially pyrazine natural product derivatives. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Graphical abstract

23 pages, 3569 KiB

Open AccessArticle

Pulicaria incisa (Lam.) DC. as a Potential Source of Antioxidant, Antibacterial, and Anti-Enzymatic Bioactive Molecules: Phytochemical Constituents, In Vitro and In Silico Pharmacological Analysis

by Mousa Alreshidi, Mohammad A. Abdulhakeem, Riadh Badraoui, Giuseppe Amato, Lucia Caputo, Laura De Martino, Filomena Nazzaro, Florinda Fratianni, Carmen Formisano, Vincenzo De Feo and Mejdi Snoussi

Molecules 2023, 28(21), 7439; https://doi.org/10.3390/molecules28217439 - 5 Nov 2023

Cited by 4 | Viewed by 1918

Abstract

Plants with medicinal benefits are a crucial source of compounds for developing drugs. This study was designed to determine the chemical composition, antibacterial, antibiofilm, antioxidant, and anti-enzymatic activities of Pulicaria incisa (Lam.) DC. We also reported the molecular interaction between identified molecules and [...] Read more.

Plants with medicinal benefits are a crucial source of compounds for developing drugs. This study was designed to determine the chemical composition, antibacterial, antibiofilm, antioxidant, and anti-enzymatic activities of Pulicaria incisa (Lam.) DC. We also reported the molecular interaction between identified molecules and several receptors associated with antimicrobial and antibiofilm activities. A total of seventeen and thirteen compounds were identified in aqueous and methanolic extracts of P. incisa, respectively. The methanolic extract yielded a higher total content of polyphenols and flavonoids of about 84.80 ± 2.8 mg GAE/g and 28.30 ± 1.2 mg QE/g, respectively. Significant antibacterial activity was recorded for both extracts, with minimum inhibitory concentration (MIC) values ranging from 30 to 36 µg/mL, and the result was comparable to the reference antibiotic control. Antibiofilm assays revealed that both extracts were able to reduce the attachment of bacterial cells to 96-well plates, but the highest antibiofilm activity was recorded against Staphylococcus aureus. The methanolic extract also showed anti-enzymatic potency and high antioxidant activity, as demonstrated by all assays used, including DPPH, FRAP, and ABTS. These results were further validated by in silico approaches, particularly the molecular interaction of the identified compounds with the targeted receptors. These findings present P. incisa as a significant source of antibacterial, antibiofilm, antioxidant, and anti-enzymatic molecules. Full article

(This article belongs to the Special Issue Natural Products: Isolation, Analysis and Biological Activity)

► Show Figures

Figure 1

16 pages, 4125 KiB

Open AccessArticle

Hybrid Zn-β-Aminoporphyrin–Carbon Nanotubes: Pyrrolidine and Direct Covalent Linkage Recognition, and Multiple-Photo Response

by Susana L. H. Rebelo, César A. T. Laia, Monika Szefczyk, Alexandra Guedes, Ana M. G. Silva and Cristina Freire

Molecules 2023, 28(21), 7438; https://doi.org/10.3390/molecules28217438 - 5 Nov 2023

Viewed by 1272

Abstract

To unveil and shape the molecular connectivity in (metallo)porphyrin–carbon nanotube hybrids are of main relevance for the multiple medicinal, photoelectronic, catalytic, and photocatalytic applications of these materials. Multi-walled carbon nanotubes (MWCNTs) were modified through 1,3-dipolar cycloaddition reactions with azomethine ylides generated in situ [...] Read more.

To unveil and shape the molecular connectivity in (metallo)porphyrin–carbon nanotube hybrids are of main relevance for the multiple medicinal, photoelectronic, catalytic, and photocatalytic applications of these materials. Multi-walled carbon nanotubes (MWCNTs) were modified through 1,3-dipolar cycloaddition reactions with azomethine ylides generated in situ and carrying pentafluorophenyl groups, followed by immobilization of the β-amino-tetraphenylporphyrinate Zn(II). The functionalities were confirmed via XPS and FTIR, whereas Raman spectroscopy showed disruptions on the graphitic carbon nanotube surface upon both steps. The functionalization extension, measured via TGA mass loss and corroborated via XPS, was 0.2 mmol·g⁻¹. Photophysical studies attest to the presence of the different porphyrin–carbon nanotube connectivity in the nanohybrid. Significantly different emission spectra and fluorescence anisotropy of 0.15–0.3 were observed upon variation of excitation wavelength. Vis-NIR absorption and flash photolysis experiments showed energy/charge transfer in the photoactivated nanohybrid. Moreover, evidence was found for direct reaction of amino groups with a carbon nanotube surface in the presence of molecular dipoles such as the zwitterionic sarcosine amino acid. Full article

(This article belongs to the Special Issue Organic Macrocycles and Related Organic-Inorganic Hybrid Derivatives: Synthesis and Biological Applications)

► Show Figures

Figure 1

22 pages, 4723 KiB

Open AccessArticle

Selected Fungicides as Potential EDC Estrogenic Micropollutants in the Environment

by Agata Jabłońska-Trypuć, Urszula Wydro, Elżbieta Wołejko, Marcin Makuła, Rafał Krętowski, Monika Naumowicz, Gabriela Sokołowska, Lluis Serra-Majem, Marzanna Cechowska-Pasko, Bożena Łozowicka, Piotr Kaczyński and Józefa Wiater

Molecules 2023, 28(21), 7437; https://doi.org/10.3390/molecules28217437 - 5 Nov 2023

Cited by 1 | Viewed by 1633

Abstract

An increasing level of pesticide exposition is being observed as a result of the consumption of large amounts of fruits, vegetables and grain products, which are key components of the vegetarian diet. Fungicides have been classified as endocrine-disrupting compounds, but their mechanisms of [...] Read more.

An increasing level of pesticide exposition is being observed as a result of the consumption of large amounts of fruits, vegetables and grain products, which are key components of the vegetarian diet. Fungicides have been classified as endocrine-disrupting compounds, but their mechanisms of action have not yet been clarified. The effect of boscalid (B), cyprodinil (C) and iprodione (I) combined with Tamoxifen (T) and 17β-estradiol (E2) on cell viability, cell proliferation, reporter gene expression, ROS content, the cell membrane’s function, cell morphology and antioxidant enzymes gene expression in MCF-7 and T47D-KBluc cell lines were investigated. The cell lines were chosen due to their response to 17β -estradiol. The selected fungicides are commonly used in Poland to protect crops against fungi. Our results revealed that the studied fungicides caused significant increases in cell viability and proliferation, and estrogenic activity was present in all studied compounds depending on their concentrations. Oxidative stress activated uncontrolled cancer cell proliferation by inducing ROS production and by inhibiting antioxidant defense. Our findings verify that the studied fungicides could possibly exhibit endocrine-disrupting properties and exposure should be avoided. Full article

(This article belongs to the Special Issue Analysis of Residues in Environmental Samples II)

► Show Figures

Figure 1

23 pages, 2215 KiB

Open AccessReview

The Role of Genistein in Mammalian Reproduction

by Gabriella Guelfi, Rolando Pasquariello, Polina Anipchenko, Camilla Capaccia, Georgia Pennarossa, Tiziana A. L. Brevini, Fulvio Gandolfi, Massimo Zerani and Margherita Maranesi

Molecules 2023, 28(21), 7436; https://doi.org/10.3390/molecules28217436 - 5 Nov 2023

Cited by 4 | Viewed by 2819

Abstract

Genistein is a natural compound belonging to flavonoids, having antioxidant, anti-inflammatory, and anti-neoplastic properties. Genistein is considered a phytoestrogen. As such, genistein can bind estrogen receptors (ERα and ERβ), although with a lower affinity than that of estradiol. Despite considerable work, the effects [...] Read more.

Genistein is a natural compound belonging to flavonoids, having antioxidant, anti-inflammatory, and anti-neoplastic properties. Genistein is considered a phytoestrogen. As such, genistein can bind estrogen receptors (ERα and ERβ), although with a lower affinity than that of estradiol. Despite considerable work, the effects of genistein are not well established yet. This review aims to clarify the role of genistein on female and male reproductive functions in mammals. In females, at a high dose, genistein diminishes the ovarian activity regulating several pathway molecules, such as topoisomerase isoform I and II, protein tyrosine kinases (v-src, Mek-4, ABL, PKC, Syk, EGFR, FGFR), ABC, CFTR, Glut1, Glut4, 5α-reductase, PPAR-γ, mitogen-activated protein kinase A, protein histidine kinase, and recently circulating RNA-miRNA. The effect of genistein on pregnancy is still controversial. In males, genistein exerts an estrogenic effect by inducing testosterone biosynthesis. The interaction of genistein with both natural and synthetic endocrine disruptors has a negative effect on testis function. The positive effect of genistein on sperm quality is still in debate. In conclusion, genistein has a potentially beneficial effect on the mechanisms regulating the reproduction of females and males. However, this is dependent on the dose, the species, the route, and the time of administration. Full article

(This article belongs to the Special Issue Biological Activity of Phenolics and Polyphenols in Nature Products)

► Show Figures

Figure 1

12 pages, 6895 KiB

Open AccessArticle

Organic LEDs Based on Bis(8-hydroxyquinoline) Zinc Derivatives with a Styryl Group

by Malgorzata Sypniewska, Monika Pokladko-Kowar, Ewa Gondek, Aleksandra Apostoluk, Piotr Kamedulski, Vitaliy Smokal, Peng Song, Junyan Liu, Robert Szczesny and Beata Derkowska-Zielinska

Molecules 2023, 28(21), 7435; https://doi.org/10.3390/molecules28217435 - 5 Nov 2023

Cited by 2 | Viewed by 1704

Abstract

For the first time, organic light-emitting diodes (OLEDs) based on bis(8-hydroxyquinoline) zinc with a styryl group (ZnStq) dispersed in poly(N-vinylcarbazole) matrix (ZnStq_R:PVK, where R = H, Cl, OCH₃) were fabricated. The ZnStq_R:PVK films made via the spin-coating method were used as [...] Read more.

For the first time, organic light-emitting diodes (OLEDs) based on bis(8-hydroxyquinoline) zinc with a styryl group (ZnStq) dispersed in poly(N-vinylcarbazole) matrix (ZnStq_R:PVK, where R = H, Cl, OCH₃) were fabricated. The ZnStq_R:PVK films made via the spin-coating method were used as the active layer in these devices. The produced OLEDs showed strong electroluminescence with yellow emissions at 590, 587 and 578 nm for the ZnStq_H:PVK, ZnStq_Cl:PVK and ZnStq_OCH₃:PVK, respectively. For all the studied thin films, the main photoluminescence emission bands were observed between 565 and 571 nm. The OLED with the ZnStq_OCH₃:PVK layer with a narrow electroluminescence spectrum was found to have sufficient color purity to produce ultra-high-resolution displays with reduced power consumption (full width at half maximum of 59 nm, maximum brightness of 2244 cd/m² and maximum current efficiency of 1.24 cd/A, with a turn-on voltage of 6.94 V and a threshold voltage of 7.35 V). To characterize the photophysical properties of the active layer, the ZnStq_R:PVK layers samples were additionally deposited on glass and silicon substrates. We found that the obtained results predestine ZnStq_R:PVK layers for use in the lighting industry in the future. Full article

(This article belongs to the Special Issue Advanced Materials for Energy and Sustainability)

► Show Figures

Graphical abstract

18 pages, 2685 KiB

Open AccessArticle

Phase Behavior and Structure of Poloxamer Block Copolymers in Protic and Aprotic Ionic Liquids

by Aikaterini Tsoutsoura, Zhiqi He and Paschalis Alexandridis

Molecules 2023, 28(21), 7434; https://doi.org/10.3390/molecules28217434 - 5 Nov 2023

Cited by 3 | Viewed by 1994

Abstract

Ionic liquids are promising media for self-assembling block copolymers in applications such as energy storage. A robust design of block copolymer formulations in ionic liquids requires fundamental knowledge of their self-organization at the nanoscale. To this end, here, we focus on modeling two-component [...] Read more.

Ionic liquids are promising media for self-assembling block copolymers in applications such as energy storage. A robust design of block copolymer formulations in ionic liquids requires fundamental knowledge of their self-organization at the nanoscale. To this end, here, we focus on modeling two-component systems comprising a Poly(ethylene oxide)-poly (propylene oxide)-Poly(ethylene oxide) (PEO-PPO-PEO) block copolymer (Pluronic P105: EO₃₇PO₅₈EO₃₇) and room temperature ionic liquids (RTILs): protic ethylammonium nitrate (EAN), aprotic ionic liquids (1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF₆), or 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF₄). Rich structural polymorphism was exhibited, including phases of micellar (sphere) cubic, hexagonal (cylinder), bicontinuous cubic, and lamellar (bilayer) lyotropic liquid crystalline (LLC) ordered structures in addition to solution regions. The characteristic scales of the structural lengths were obtained using small-angle X-ray scattering (SAXS) data analysis. On the basis of phase behavior and structure, the effects of the ionic liquid solvent on block copolymer organization were assessed and contrasted to those of molecular solvents, such as water and formamide. Full article

(This article belongs to the Special Issue Colloids and Polymers: An Issue in Honor of Professor Björn Lindman)

► Show Figures

Figure 1

18 pages, 4868 KiB

Open AccessReview

Nocardioides: “Specialists” for Hard-to-Degrade Pollutants in the Environment

by Yecheng Ma, Jinxiu Wang, Yang Liu, Xinyue Wang, Binglin Zhang, Wei Zhang, Tuo Chen, Guangxiu Liu, Lingui Xue and Xiaowen Cui

Molecules 2023, 28(21), 7433; https://doi.org/10.3390/molecules28217433 - 5 Nov 2023

Cited by 22 | Viewed by 2732

Abstract

Nocardioides, a genus belonging to Actinomycetes, can endure various low-nutrient conditions. It can degrade pollutants using multiple organic materials such as carbon and nitrogen sources. The characteristics and applications of Nocardioides are described in detail in this review, with emphasis on [...] Read more.

Nocardioides, a genus belonging to Actinomycetes, can endure various low-nutrient conditions. It can degrade pollutants using multiple organic materials such as carbon and nitrogen sources. The characteristics and applications of Nocardioides are described in detail in this review, with emphasis on the degradation of several hard-to-degrade pollutants by using Nocardioides, including aromatic compounds, hydrocarbons, haloalkanes, nitrogen heterocycles, and polymeric polyesters. Nocardioides has unique advantages when it comes to hard-to-degrade pollutants. Compared to other strains, Nocardioides has a significantly higher degradation rate and requires less time to break down substances. This review can be a theoretical basis for developing Nocardioides as a microbial agent with significant commercial and application potential. Full article

► Show Figures

Graphical abstract

14 pages, 7434 KiB

Open AccessArticle

Particle Size Effect of Cyetpyrafen Formulation in the Pesticide Transmission Process and Its Impact on Biological Activity

by Lu Yu, He Liu, Miao Yu, Qi Zhang, Jingyu Chou and Yuanhua Wu

Molecules 2023, 28(21), 7432; https://doi.org/10.3390/molecules28217432 - 5 Nov 2023

Cited by 1 | Viewed by 1664

Abstract

Cyetpyrafen is a compound that lacks inherent uptake and systemic translocation activity. If mites do not come into direct contact with the pesticide solution on leaves, the efficacy cannot be achieved. Controlling the particle size can potentially play a crucial role in the [...] Read more.

Cyetpyrafen is a compound that lacks inherent uptake and systemic translocation activity. If mites do not come into direct contact with the pesticide solution on leaves, the efficacy cannot be achieved. Controlling the particle size can potentially play a crucial role in the manifestation of efficacy. In this study, high-throughput formulation technology was used to systematically screen a large number of adjuvants to obtain cyetpyrafen formulations. The particle size of the active ingredient in the formulation was measured. By examining the dynamic light scattering and contact angle, we simulated the actual process of the efficacy transmission of cyetpyrafen formulations against Tetranychus cinnabarinus. Our results showed that the activity of cyetpyrafen increases as the particle size decreases, suggesting that reducing the particle size can enhance the coverage and deposition on crop leaves, and further improve the dispersion efficiency and enhance spreading capabilities. Furthermore, controlling the particle size at 160 nm resulted in an LC₅₀ value of 0.2026, which is approximately double than that of the commercial product. As a novel pesticide for mites, our study presents the most effective cyetpyrafen formulation in practice. Our findings provide valuable insights into controlling other mite species that pose a threat to agricultural products. Full article

► Show Figures

Figure 1

16 pages, 2205 KiB

Open AccessReview

The Interactions of Soy Protein and Wheat Gluten for the Development of Meat-like Fibrous Structure

by Yu Peng, Dandan Zhao, Mo Li, Xin Wen and Yuanying Ni

Molecules 2023, 28(21), 7431; https://doi.org/10.3390/molecules28217431 - 4 Nov 2023

Cited by 5 | Viewed by 3787

Abstract

Consumers who are environmentally and health conscious are increasingly looking for plant-based alternatives to replace animal-based products in their daily diets. Among these alternatives, there is a growing demand for meat analogues that closely resemble the taste and texture of meat. As a [...] Read more.

Consumers who are environmentally and health conscious are increasingly looking for plant-based alternatives to replace animal-based products in their daily diets. Among these alternatives, there is a growing demand for meat analogues that closely resemble the taste and texture of meat. As a result, significant efforts have been dedicated to developing meat analogues with a desirable meat-like structure. Currently, soy protein and wheat gluten are the main ingredients used for producing these meat analogues due to their availability and unique functionalities. This study observed that high moisture extrusion at moisture levels of 50–80% has become a common approach for creating fibrous structures, with soy protein and wheat gluten being considered incompatible proteins. After the structuring process, they form two-phase filled gels, with wheat gluten acting as the continuous phase and soy protein serving as a filler material. Moreover, the formation of soy protein and wheat gluten networks relies on a combination of covalent and non-covalent interaction bonds, including hydrogen bonds that stabilize the protein networks, hydrophobic interactions governing protein chain associations during thermo-mechanical processes, and disulfide bonds that potentially contribute to fibrous structure formation. This review provides case studies and examples that demonstrate how specific processing conditions can improve the overall structure, aiming to serve as a valuable reference for further research and the advancement of fibrous structures. Full article

(This article belongs to the Special Issue Physicochemical Interactions in Food)

► Show Figures

Figure 1

22 pages, 697 KiB

Open AccessReview

Recent Progress in Mass Spectrometry-Based Metabolomics in Major Depressive Disorder Research

by Mingxia Liu, Wen Ma, Yi He, Zuoli Sun and Jian Yang

Molecules 2023, 28(21), 7430; https://doi.org/10.3390/molecules28217430 - 4 Nov 2023

Cited by 1 | Viewed by 2957

Abstract

Major depressive disorder (MDD) is a serious mental illness with a heavy social burden, but its underlying molecular mechanisms remain unclear. Mass spectrometry (MS)-based metabolomics is providing new insights into the heterogeneous pathophysiology, diagnosis, treatment, and prognosis of MDD by revealing multi-parametric biomarker [...] Read more.

Major depressive disorder (MDD) is a serious mental illness with a heavy social burden, but its underlying molecular mechanisms remain unclear. Mass spectrometry (MS)-based metabolomics is providing new insights into the heterogeneous pathophysiology, diagnosis, treatment, and prognosis of MDD by revealing multi-parametric biomarker signatures at the metabolite level. In this comprehensive review, recent developments of MS-based metabolomics in MDD research are summarized from the perspective of analytical platforms (liquid chromatography-MS, gas chromatography-MS, supercritical fluid chromatography-MS, etc.), strategies (untargeted, targeted, and pseudotargeted metabolomics), key metabolite changes (monoamine neurotransmitters, amino acids, lipids, etc.), and antidepressant treatments (both western and traditional Chinese medicines). Depression sub-phenotypes, comorbid depression, and multi-omics approaches are also highlighted to stimulate further advances in MS-based metabolomics in the field of MDD research. Full article

(This article belongs to the Special Issue Mass Spectrometry for Biomedical and Food Analysis)

► Show Figures

Graphical abstract

23 pages, 2381 KiB

Open AccessReview

Polyamine-Derived Aminoaldehydes and Acrolein: Cytotoxicity, Reactivity and Analysis of the Induced Protein Modifications

by Marek Šebela and Michaela Rašková

Molecules 2023, 28(21), 7429; https://doi.org/10.3390/molecules28217429 - 4 Nov 2023

Cited by 3 | Viewed by 2311

Abstract

Polyamines participate in the processes of cell growth and development. The degradation branch of their metabolism involves amine oxidases. The oxidation of spermine, spermidine and putrescine releases hydrogen peroxide and the corresponding aminoaldehyde. Polyamine-derived aminoaldehydes have been found to be cytotoxic, and they [...] Read more.

Polyamines participate in the processes of cell growth and development. The degradation branch of their metabolism involves amine oxidases. The oxidation of spermine, spermidine and putrescine releases hydrogen peroxide and the corresponding aminoaldehyde. Polyamine-derived aminoaldehydes have been found to be cytotoxic, and they represent the subject of this review. 3-aminopropanal disrupts the lysosomal membrane and triggers apoptosis or necrosis in the damaged cells. It is implicated in the pathogenesis of cerebral ischemia. Furthermore, 3-aminopropanal yields acrolein through the elimination of ammonia. This reactive aldehyde is also generated by the decomposition of aminoaldehydes produced in the reaction of serum amine oxidase with spermidine or spermine. In addition, acrolein is a common environmental pollutant. It causes covalent modifications of proteins, including carbonylation, the production of Michael-type adducts and cross-linking, and it has been associated with inflammation-related diseases. APAL and acrolein are detoxified by aldehyde dehydrogenases and other mechanisms. High-performance liquid chromatography, immunochemistry and mass spectrometry have been largely used to analyze the presence of polyamine-derived aminoaldehydes and protein modifications elicited by their effect. However, the main and still open challenge is to find clues for discovering clear linkages between aldehyde-induced modifications of specific proteins and the development of various diseases. Full article

(This article belongs to the Special Issue Review Papers in Analytical Chemistry)

► Show Figures

Graphical abstract

18 pages, 1834 KiB

Open AccessArticle

Aza Analogs of the TRPML1 Inhibitor Estradiol Methyl Ether (EDME)

by Philipp Rühl and Franz Bracher

Molecules 2023, 28(21), 7428; https://doi.org/10.3390/molecules28217428 - 4 Nov 2023

Cited by 1 | Viewed by 1240

Abstract

Estradiol methyl ether (EDME) has recently been described by us as a very potent and subtype-specific inhibitor of the lysosomal cation channel TRPML1. Following the principle of bioisosteres, we worked out efficient synthetic approaches to ring-A aza-analogs of EDME, namely a [...] Read more.

Estradiol methyl ether (EDME) has recently been described by us as a very potent and subtype-specific inhibitor of the lysosomal cation channel TRPML1. Following the principle of bioisosteres, we worked out efficient synthetic approaches to ring-A aza-analogs of EDME, namely a methoxypyridine and a methoxypyrimidine analog. Both target compounds were obtained in good overall yields in six and eight steps starting from 19-nortestosterone via the oxidative cleavage of ring A followed over several intermediates and with the use of well-selected protective groups by re-cyclization to provide the desired hetero-analogs. The methoxypyridine analog largely retained its TRPML1-inhibitory activity, whereas the methoxypyrimidine analog significantly lost activity. Full article

(This article belongs to the Special Issue Steroid Compounds with Potential Biological Activity)

► Show Figures

Figure 1

23 pages, 7944 KiB

Open AccessArticle

Novel 1,2,4-Triazole- and Tetrazole-Containing 4H-Thiopyrano[2,3-b]quinolines: Synthesis Based on the Thio-Michael/aza-Morita–Baylis–Hillman Tandem Reaction and Investigation of Antiviral Activity

by Andrey V. Khramchikhin, Mariya A. Skryl’nikova, Maxim A. Gureev, Vladimir V. Zarubaev, Iana L. Esaulkova, Polina A. Ilyina, Oussama Abdelhamid Mammeri, Dar’ya V. Spiridonova, Yuri B. Porozov and Vladimir A. Ostrovskii

Molecules 2023, 28(21), 7427; https://doi.org/10.3390/molecules28217427 - 4 Nov 2023

Cited by 1 | Viewed by 1377

Abstract

A novel method for synthesizing 1,2,4-triazole- and tetrazole-containing 4H-thiopyrano[2,3-b]quinolines using a new combination of the thio-Michael and aza-Morita–Baylis–Hillman reactions was developed. Target compounds were evaluated for their cytotoxicities and antiviral activities against influenza A/Puerto Rico/8/34 virus in MDCK cells. [...] Read more.

A novel method for synthesizing 1,2,4-triazole- and tetrazole-containing 4H-thiopyrano[2,3-b]quinolines using a new combination of the thio-Michael and aza-Morita–Baylis–Hillman reactions was developed. Target compounds were evaluated for their cytotoxicities and antiviral activities against influenza A/Puerto Rico/8/34 virus in MDCK cells. The compounds showed low toxicity and some exhibited moderate antiviral activity. Molecular docking identified the M2 channel and polymerase basic protein 2 as potential targets. We observed that the antiviral activity of thiopyrano[2,3-b]quinolines is notably affected by both the nature and position of the substituent within the tetrazole ring, as well as the substituent within the benzene moiety of quinoline. These findings contribute to the further search for new antiviral agents against influenza A viruses among derivatives of thiopyrano[2,3-b]quinoline. Full article

(This article belongs to the Special Issue Triazoles and Tetrazoles: Current Status and Perspective)

► Show Figures

Graphical abstract

13 pages, 1903 KiB

Open AccessArticle

Solvent and Substituent Size Influence on the Cyclochiral Rigidity of Aminomethylene Derivatives of Resorcin[4]arene

by Waldemar Iwanek

Molecules 2023, 28(21), 7426; https://doi.org/10.3390/molecules28217426 - 4 Nov 2023

Viewed by 1003

Abstract

Resorcin[4]arenes (R[4]A) are a group of macrocyclic compounds whose peculiar feature is the presence of eight hydroxyl groups in their structure. The directional formation of intramolecular hydrogen bonds with their participation leads to the formation of a cyclochiral racemic mixture of these compounds. [...] Read more.

Resorcin[4]arenes (R[4]A) are a group of macrocyclic compounds whose peculiar feature is the presence of eight hydroxyl groups in their structure. The directional formation of intramolecular hydrogen bonds with their participation leads to the formation of a cyclochiral racemic mixture of these compounds. Their stability strongly depends on the substituent and especially the environment in which they are located. The paper discusses the cyclochiral nature of aminomethylene derivatives of R[4]A (AMD-R[4]A). Their cyclochiral rigidity in non-polar solvents has been shown. The influence of the size of the alkyl groups in the amino substituents of AMD-R[4]A on their cyclochiral nature was noted. To calculate the reaction paths for their racemization, the nudged elastic band (NEB) method was employed using the semi-empirical DFT (GFN1-xTB) approach. The calculated activation barrier energies for their racemization in chloroform, obtained through various semi-empirical quantum chemical methods (SE), Hartree–Fock (HF), and density functionals theory (DFT), show good correlation with experimental observations. Among the tested methods, the B38LYP-D4 method is highly recommended due to its fast computational speed and accuracy, which is comparable to the time-consuming double-hybrid DH-revDSD-PBEP86 approach. Full article

(This article belongs to the Section Cross-Field Chemistry)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Molecules, Volume 28, Issue 21 (November-1 2023) – 220 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI