Molecules

15 pages, 2376 KiB

Open AccessArticle

Potential Immunogenic Activity of Computationally Designed mRNA- and Peptide-Based Prophylactic Vaccines against MERS, SARS-CoV, and SARS-CoV-2: A Reverse Vaccinology Approach

by Taimoor Khan, Abbas Khan, Jawad Khaliq Ansari, Muzammil Hasan Najmi, Dong-Qing Wei, Khalid Muhammad and Yasir Waheed

Molecules 2022, 27(7), 2375; https://doi.org/10.3390/molecules27072375 - 6 Apr 2022

Cited by 17 | Viewed by 3067

Abstract

The continued emergence of human coronaviruses (hCoVs) in the last few decades has posed an alarming situation and requires advanced cross-protective strategies against these pandemic viruses. Among these, Middle East Respiratory Syndrome coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute [...] Read more.

The continued emergence of human coronaviruses (hCoVs) in the last few decades has posed an alarming situation and requires advanced cross-protective strategies against these pandemic viruses. Among these, Middle East Respiratory Syndrome coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) have been highly associated with lethality in humans. Despite the challenges posed by these viruses, it is imperative to develop effective antiviral therapeutics and vaccines for these human-infecting viruses. The proteomic similarity between the receptor-binding domains (RBDs) among the three viral species offers a potential target for advanced cross-protective vaccine designs. In this study, putative immunogenic epitopes including Cytotoxic T Lymphocytes (CTLs), Helper T Lymphocytes (HTLs), and Beta-cells (B-cells) were predicted for each RBD-containing region of the three highly pathogenic hCoVs. This was followed by the structural organization of peptide- and mRNA-based prophylactic vaccine designs. The validated 3D structures of these epitope-based vaccine designs were subjected to molecular docking with human TLR4. Furthermore, the CTL and HTL epitopes were processed for binding with respective human Lymphocytes Antigens (HLAs). In silico cloning designs were obtained for the prophylactic vaccine designs and may be useful in further experimental designs. Additionally, the epitope-based vaccine designs were evaluated for immunogenic activity through immune simulation. Further studies may clarify the safety and efficacy of these prophylactic vaccine designs through experimental testing against these human-pathogenic coronaviruses. Full article

(This article belongs to the Special Issue Structural Biology Approach in Drug Discovery)

► Show Figures

Figure 1

22 pages, 28004 KiB

Open AccessReview

Progress in Electrohydrodynamic Atomization Preparation of Energetic Materials with Controlled Microstructures

by Lihong Chen, Chengbo Ru, Hongguo Zhang, Yanchun Zhang, Hongxing Wang, Xiuli Hu and Gang Li

Molecules 2022, 27(7), 2374; https://doi.org/10.3390/molecules27072374 - 6 Apr 2022

Cited by 9 | Viewed by 3000

Abstract

Constructing ingenious microstructures, such as core–shell, laminate, microcapsule and porous microstructures, is an efficient strategy for tuning the combustion behaviors and thermal stability of energetic materials (EMs). Electrohydrodynamic atomization (EHDA), which includes electrospray and electrospinning, is a facile and versatile technique that can [...] Read more.

Constructing ingenious microstructures, such as core–shell, laminate, microcapsule and porous microstructures, is an efficient strategy for tuning the combustion behaviors and thermal stability of energetic materials (EMs). Electrohydrodynamic atomization (EHDA), which includes electrospray and electrospinning, is a facile and versatile technique that can be used to process bulk materials into particles, fibers, films and three-dimensional (3D) structures with nanoscale feature sizes. However, the application of EHDA in preparing EMs is still in its initial development. This review summarizes the progress of research on EMs prepared by EHDA over the last decade. The morphology and internal structure of the produced materials can be easily altered by varying the operation and precursor parameters. The prepared EMs composed of zero-dimensional (0D) particles, one-dimensional (1D) fibers and two-dimensional (2D) films possess precise microstructures with large surface areas, uniformly dispersed components and narrow size distributions and show superior energy release rates and combustion performances. We also explore the reasons why the fabrication of 3D EM structures by EHDA is still lacking. Finally, we discuss development challenges that impede this field from moving out of the laboratory and into practical application. Full article

(This article belongs to the Special Issue Research and Application of Nanoenergetic Materials)

► Show Figures

Graphical abstract

11 pages, 10968 KiB

Open AccessEditor’s ChoiceArticle

Synthesis and Reactivity of Manganese Complexes Bearing Anionic PNP- and PCP-Type Pincer Ligands toward Nitrogen Fixation

by Shogo Kuriyama, Shenglan Wei, Takeru Kato and Yoshiaki Nishibayashi

Molecules 2022, 27(7), 2373; https://doi.org/10.3390/molecules27072373 - 6 Apr 2022

Cited by 5 | Viewed by 3230

Abstract

A series of manganese complexes bearing an anionic pyrrole-based PNP-type pincer ligand and an anionic benzene-based PCP-type pincer ligand is synthesized and characterized. The reactivity of these complexes toward ammonia formation and silylamine formation from dinitrogen under mild conditions is evaluated to produce [...] Read more.

A series of manganese complexes bearing an anionic pyrrole-based PNP-type pincer ligand and an anionic benzene-based PCP-type pincer ligand is synthesized and characterized. The reactivity of these complexes toward ammonia formation and silylamine formation from dinitrogen under mild conditions is evaluated to produce only stoichiometric amounts of ammonia and silylamine, probably because the manganese pincer complexes are unstable under reducing conditions. Full article

(This article belongs to the Special Issue Design Strategies for Metal Complexes that Activate Bio-Related Small Molecules)

► Show Figures

Figure 1

22 pages, 2644 KiB

Open AccessArticle

Secondary Metabolism Rearrangements in Linum usitatissimum L. after Biostimulation of Roots with COS Oligosaccharides from Fungal Cell Wall

by Redouan Elboutachfaiti, Roland Molinié, David Mathiron, Yannis Maillot, Jean-Xavier Fontaine, Serge Pilard, Anthony Quéro, Clément Brasselet, Marguerite Dols-Lafargue, Cédric Delattre and Emmanuel Petit

Molecules 2022, 27(7), 2372; https://doi.org/10.3390/molecules27072372 - 6 Apr 2022

Cited by 6 | Viewed by 3123

Abstract

In vitro culture of flax (Linum usitatissimum L.) was exposed to chitosan oligosaccharides (COS) in order to investigate the effects on the growth and secondary metabolites content in roots and shoots. COS are fragments of chitosan released from the fungal cell wall [...] Read more.

In vitro culture of flax (Linum usitatissimum L.) was exposed to chitosan oligosaccharides (COS) in order to investigate the effects on the growth and secondary metabolites content in roots and shoots. COS are fragments of chitosan released from the fungal cell wall during plant–pathogen interactions. They can be perceived by the plant as pathogen-associated signals, mediating local and systemic innate immune responses. In the present study, we report a novel COS oligosaccharide fraction with a degree of polymerization (DP) range of 2–10, which was produced from fungal chitosan by a thermal degradation method and purified by an alcohol-precipitation process. COS was dissolved in hydroponic medium at two different concentrations (250 and 500 mg/L) and applied to the roots of growing flax seedlings. Our observations indicated that the growth of roots and shoots decreased markedly in COS-treated flax seedlings compared to the control. In addition, the results of a metabolomics analysis showed that COS treatment induced the accumulation of (neo)lignans locally at roots, flavones luteolin C-glycosides, and chlorogenic acid in systemic responses in the shoots of flax seedlings. These phenolic compounds have been previously reported to exhibit a strong antioxidant and antimicrobial activities. COS oligosaccharides, under the conditions applied in this study (high dose treatment with a much longer exposure time), can be used to indirectly trigger metabolic response modifications in planta, especially secondary metabolism, because during fungal pathogen attack, COS oligosaccharides are among the signals exchanged between the pathogen and host plant. Full article

(This article belongs to the Special Issue Molecules in 2022)

► Show Figures

Graphical abstract

13 pages, 2135 KiB

Open AccessCommunication

Functional Protein Composition in Femoral Glands of Sand Lizards (Lacerta agilis)

by Alejandro Ibáñez, Bozena Skupien-Rabian, Urszula Jankowska, Sylwia Kędracka-Krok, Bartłomiej Zając and Maciej Pabijan

Molecules 2022, 27(7), 2371; https://doi.org/10.3390/molecules27072371 - 6 Apr 2022

Cited by 7 | Viewed by 2840

Abstract

Proteins are ubiquitous macromolecules that display a vast repertoire of chemical and enzymatic functions, making them suitable candidates for chemosignals, used in intraspecific communication. Proteins are present in the skin gland secretions of vertebrates but their identity, and especially, their functions, remain largely [...] Read more.

Proteins are ubiquitous macromolecules that display a vast repertoire of chemical and enzymatic functions, making them suitable candidates for chemosignals, used in intraspecific communication. Proteins are present in the skin gland secretions of vertebrates but their identity, and especially, their functions, remain largely unknown. Many lizard species possess femoral glands, i.e., epidermal organs primarily involved in the production and secretion of chemosignals, playing a pivotal role in mate choice and intrasexual communication. The lipophilic fraction of femoral glands has been well studied in lizards. In contrast, proteins have been the focus of only a handful of investigations. Here, we identify and describe inter-individual expression patterns and the functionality of proteins present in femoral glands of male sand lizards (Lacerta agilis) by applying mass spectrometry-based proteomics. Our results show that the total number of proteins varied substantially among individuals. None of the identified femoral gland proteins could be directly linked to chemical communication in lizards, although this result hinges on protein annotation in databases in which squamate semiochemicals are poorly represented. In contrast to our expectations, the proteins consistently expressed across individuals were related to the immune system, antioxidant activity and lipid metabolism as their main functions, showing that proteins in reptilian epidermal glands may have other functions besides chemical communication. Interestingly, we found expression of the Major Histocompatibility Complex (MHC) among the multiple and diverse biological processes enriched in FGs, tentatively supporting a previous hypothesis that MHC was coopted for semiochemical function in sand lizards, specifically in mate recognition. Our study shows that mass spectrometry-based proteomics are a powerful tool for characterizing and deciphering the role of proteins secreted by skin glands in non-model vertebrates. Full article

(This article belongs to the Section Chemical Biology)

► Show Figures

Figure 1

16 pages, 2619 KiB

Open AccessArticle

Molecular Dynamics and MM-PBSA Analysis of the SARS-CoV-2 Gamma Variant in Complex with the hACE-2 Receptor

by Maurizio Cavani, Walter Arnaldo Riofrío and Marcelino Arciniega

Molecules 2022, 27(7), 2370; https://doi.org/10.3390/molecules27072370 - 6 Apr 2022

Cited by 9 | Viewed by 3999

Abstract

The SARS-CoV-2 virus, since its appearance in 2019, has caused millions of cases and deaths. To date, there is no effective treatment or a vaccine that is fully protective. Despite the efforts made by governments and health institutions around the globe to control [...] Read more.

The SARS-CoV-2 virus, since its appearance in 2019, has caused millions of cases and deaths. To date, there is no effective treatment or a vaccine that is fully protective. Despite the efforts made by governments and health institutions around the globe to control its propagation, the evolution of the virus has accelerated, diverging into hundreds of variants. However, not all of them are variants of concern (VoC’s). VoC’s have appeared in different regions and throughout the two years of the pandemic they have spread around the world. Specifically, in South America, the gamma variant (previously known as P.1) appeared in early 2021, bringing with it a second wave of infections. This variant contains the N501Y, E484K and K417T mutations in the receptor binding domain (RBD) of the spike protein. Although these mutations have been described experimentally, there is still no clarity regarding their role in the stabilization of the complex with the human angiotensin converting enzyme 2 (hACE-2) receptor. In this article we dissect the influence of mutations on the interaction with the hACE-2 receptor using molecular dynamics and estimations of binding affinity through a screened version of the molecular mechanics Poisson Boltzmann surface area (MM-PBSA) and interaction entropy. Our results indicate that mutations E484K and K417T compensate each other in terms of binding affinity, while the mutation N501Y promotes a more convoluted effect. This effect consists in the adoption of a cis configuration in the backbone of residue Y495 within the RBD, which in turn promotes polar interactions with the hACE-2 receptor. These results not only correlate with experimental observations and complement previous knowledge, but also expose new features associated with the specific contribution of concerned mutations. Additionally, we propose a recipe to assess the residue-specific contribution to the interaction entropy. Full article

(This article belongs to the Section Chemical Biology)

► Show Figures

Figure 1

12 pages, 3505 KiB

Open AccessArticle

Intermolecular Halogen Bond Detected in Racemic and Optically Pure N-C Axially Chiral 3-(2-Halophenyl)quinazoline-4-thione Derivatives

by Ryosuke Matsui, Erina Niijima, Tomomi Imai, Hiroyuki Kobayashi, Akiko Hori, Azusa Sato, Yuko Nakamura and Osamu Kitagawa

Molecules 2022, 27(7), 2369; https://doi.org/10.3390/molecules27072369 - 6 Apr 2022

Cited by 4 | Viewed by 2781

Abstract

The halogen bond has been widely used as an important supramolecular tool in various research areas. However, there are relatively few studies on halogen bonding related to molecular chirality. 3-(2-Halophenyl)quinazoline-4-thione derivatives have stable atropisomeric structures due to the rotational restriction around an N-C [...] Read more.

The halogen bond has been widely used as an important supramolecular tool in various research areas. However, there are relatively few studies on halogen bonding related to molecular chirality. 3-(2-Halophenyl)quinazoline-4-thione derivatives have stable atropisomeric structures due to the rotational restriction around an N-C single bond. In X-ray single crystal structures of the racemic and optically pure N-C axially chiral quinazoline-4-thiones, we found that different types of intermolecular halogen bonds (C=S⋯X) are formed. That is, in the racemic crystals, the intermolecular halogen bond between the ortho-halogen atom and sulfur atom was found to be oriented in a periplanar conformation toward the thiocarbonyl plane, leading to a syndiotactic zig-zag array. On the other hand, the halogen bond in the enantiomerically pure crystals was oriented orthogonally toward the thiocarbonyl plane, resulting in the formation of a homochiral dimer. These results indicate that the corresponding racemic and optically pure forms in chiral molecules are expected to display different halogen bonding properties, respectively, and should be separately studied as different chemical entities. Full article

(This article belongs to the Special Issue Molecules in 2022)

► Show Figures

Figure 1

27 pages, 3589 KiB

Open AccessArticle

Volumetric Scalability of Microfluidic and Semi-Batch Silk Nanoprecipitation Methods

by Saphia A. L. Matthew, Refaya Rezwan, Yvonne Perrie and F. Philipp Seib

Molecules 2022, 27(7), 2368; https://doi.org/10.3390/molecules27072368 - 6 Apr 2022

Cited by 10 | Viewed by 2966

Abstract

Silk fibroin nanoprecipitation by organic desolvation in semi-batch and microfluidic formats provides promising bottom-up routes for manufacturing narrow polydispersity, spherical silk nanoparticles. The translation of silk nanoparticle production to pilot, clinical, and industrial scales can be aided through insight into the property drifts [...] Read more.

Silk fibroin nanoprecipitation by organic desolvation in semi-batch and microfluidic formats provides promising bottom-up routes for manufacturing narrow polydispersity, spherical silk nanoparticles. The translation of silk nanoparticle production to pilot, clinical, and industrial scales can be aided through insight into the property drifts incited by nanoprecipitation scale-up and the identification of critical process parameters to maintain throughout scaling. Here, we report the reproducibility of silk nanoprecipitation on volumetric scale-up in low-shear, semi-batch systems and estimate the reproducibility of chip parallelization for volumetric scale-up in a high shear, staggered herringbone micromixer. We showed that silk precursor feeds processed in an unstirred semi-batch system (mixing time > 120 s) displayed significant changes in the nanoparticle physicochemical and crystalline properties following a 12-fold increase in volumetric scale between 1.8 and 21.9 mL while the physicochemical properties stayed constant following a further 6-fold increase in scale to 138 mL. The nanoparticle physicochemical properties showed greater reproducibility after a 6-fold volumetric scale-up when using lower mixing times of greater similarity (8.4 s and 29.4 s) with active stirring at 400 rpm, indicating that the bulk mixing time and average shear rate should be maintained during volumetric scale-up. Conversely, microfluidic manufacture showed high between-batch repeatability and between-chip reproducibility across four participants and microfluidic chips, thereby strengthening chip parallelization as a production strategy for silk nanoparticles at pilot, clinical, and industrial scales. Full article

(This article belongs to the Special Issue The Chemical Properties of Silk Raw Materials)

► Show Figures

Figure 1

18 pages, 1723 KiB

Open AccessArticle

Structural Properties of Phenylalanine-Based Dimers Revealed Using IR Action Spectroscopy

by Iuliia Stroganova, Sjors Bakels and Anouk M. Rijs

Molecules 2022, 27(7), 2367; https://doi.org/10.3390/molecules27072367 - 6 Apr 2022

Cited by 3 | Viewed by 2710

Abstract

Peptide segments with phenylalanine residues are commonly found in proteins that are related to neurodegenerative diseases. However, the self-assembly of phenylalanine-based peptides can be also functional. Peptides containing phenylalanine residues with different side caps, composition, and chemical alteration can form different types of [...] Read more.

Peptide segments with phenylalanine residues are commonly found in proteins that are related to neurodegenerative diseases. However, the self-assembly of phenylalanine-based peptides can be also functional. Peptides containing phenylalanine residues with different side caps, composition, and chemical alteration can form different types of nanostructures that find many applications in technology and medicine. Various studies have been performed in order to explain the remarkable stability of the resulting nanostructures. Here, we study the early stages of self-assembly of two phenylalanine derived peptides in the gas phase using IR action spectroscopy. Our focus lies on the identification of the key intra- and intermolecular interactions that govern the formation of the dimers. The far-IR region allowed us to distinguish between structural families and to assign the 2-(2-amino-2-phenylacetamido)-2-phenylacetic acid (PhgPhg) dimer to a very symmetric structure with two intermolecular hydrogen bonds and its aromatic rings folded away from the backbone. By comparison with the phenylalanine-based peptide cyclic L-phenylalanyl-L-phenylalanine (cyclo-FF), we found that the linear FF dimer likely adopts a less ordered structure. However, when one more phenylalanine residue is added (FFF), a more structurally organized dimer is formed with several intermolecular hydrogen bonds. Full article

(This article belongs to the Special Issue Rotational and Vibrational Probes of Biomolecular Structure and Dynamics)

► Show Figures

Figure 1

21 pages, 2915 KiB

Open AccessReview

The Pharmacological Potential of Adenosine A_2A Receptor Antagonists for Treating Parkinson’s Disease

by Akihisa Mori, Jiang-Fan Chen, Shinichi Uchida, Cecile Durlach, Shelby M. King and Peter Jenner

Molecules 2022, 27(7), 2366; https://doi.org/10.3390/molecules27072366 - 6 Apr 2022

Cited by 26 | Viewed by 5938

Abstract

The adenosine A_2A receptor subtype is recognized as a non-dopaminergic pharmacological target for the treatment of neurodegenerative disorders, notably Parkinson’s disease (PD). The selective A_2A receptor antagonist istradefylline is approved in the US and Japan as an adjunctive treatment to levodopa/decarboxylase [...] Read more.

The adenosine A_2A receptor subtype is recognized as a non-dopaminergic pharmacological target for the treatment of neurodegenerative disorders, notably Parkinson’s disease (PD). The selective A_2A receptor antagonist istradefylline is approved in the US and Japan as an adjunctive treatment to levodopa/decarboxylase inhibitors in adults with PD experiencing OFF episodes or a wearing-off phenomenon; however, the full potential of this drug class remains to be explored. In this article, we review the pharmacology of adenosine A_2A receptor antagonists from the perspective of the treatment of both motor and non-motor symptoms of PD and their potential for disease modification. Full article

(This article belongs to the Special Issue Purinergic Signaling: Targeting GPCRs, Ion Channels and Enzymes—A Theme Issue in Honor of Dr. Kenneth A. Jacobson)

► Show Figures

Figure 1

23 pages, 1625 KiB

Open AccessReview

Flavonoids in Treatment of Chronic Kidney Disease

by Yi-Ling Cao, Ji-Hong Lin, Hans-Peter Hammes and Chun Zhang

Molecules 2022, 27(7), 2365; https://doi.org/10.3390/molecules27072365 - 6 Apr 2022

Cited by 35 | Viewed by 7127

Abstract

Chronic kidney disease (CKD) is a progressive systemic disease, which changes the function and structure of the kidneys irreversibly over months or years. The final common pathological manifestation of chronic kidney disease is renal fibrosis and is characterized by glomerulosclerosis, tubular atrophy, and [...] Read more.

Chronic kidney disease (CKD) is a progressive systemic disease, which changes the function and structure of the kidneys irreversibly over months or years. The final common pathological manifestation of chronic kidney disease is renal fibrosis and is characterized by glomerulosclerosis, tubular atrophy, and interstitial fibrosis. In recent years, numerous studies have reported the therapeutic benefits of natural products against modern diseases. Substantial attention has been focused on the biological role of polyphenols, in particular flavonoids, presenting broadly in plants and diets, referring to thousands of plant compounds with a common basic structure. Evidence-based pharmacological data have shown that flavonoids play an important role in preventing and managing CKD and renal fibrosis. These compounds can prevent renal dysfunction and improve renal function by blocking or suppressing deleterious pathways such as oxidative stress and inflammation. In this review, we summarize the function and beneficial properties of common flavonoids for the treatment of CKD and the relative risk factors of CKD. Full article

(This article belongs to the Special Issue Animal Models of Human Diseases and Their Potential Therapies of Natural Products or Pure Components)

► Show Figures

Figure 1

16 pages, 3066 KiB

Open AccessArticle

Synthesis of Novel C/D Ring Modified Bile Acids

by Roselis A. Landaeta Aponte, Andreas Luxenburger, Scott A. Cameron, Alex Weymouth-Wilson, Richard H. Furneaux, Lawrence D. Harris and Benjamin J. Compton

Molecules 2022, 27(7), 2364; https://doi.org/10.3390/molecules27072364 - 6 Apr 2022

Cited by 2 | Viewed by 2713

Abstract

Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards [...] Read more.

Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro–furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation. Full article

(This article belongs to the Special Issue Organic Synthesis in Drug Discovery)

► Show Figures

Graphical abstract

8 pages, 539 KiB

Open AccessArticle

Bioactive Terphenyls Isolated from the Antarctic Lichen Stereocaulon alpinum

by Kim-Hoa Phi, Min-Ji Shin, Seulah Lee, Jae Eun So, Ji Hee Kim, Sung-Suk Suh, Man Hyung Koo, Seung Chul Shin, Jin-Hyoung Kim, Jun Hyuck Lee and Ui Joung Youn

Molecules 2022, 27(7), 2363; https://doi.org/10.3390/molecules27072363 - 6 Apr 2022

Cited by 4 | Viewed by 2424

Abstract

Three p-terphenyls (2–4)—2-hydroxy-3,5-dimethoxy-p-terphenyl (2), 2-hydroxy-3,6-dimethoxy-p-terphenyl (3), and 2,3,5,6-tetramethoxy-p-terphenyl (4)—were isolated for the first time as natural products along with seven known compounds (1, 5 [...] Read more.

Three p-terphenyls (2–4)—2-hydroxy-3,5-dimethoxy-p-terphenyl (2), 2-hydroxy-3,6-dimethoxy-p-terphenyl (3), and 2,3,5,6-tetramethoxy-p-terphenyl (4)—were isolated for the first time as natural products along with seven known compounds (1, 5–10) from the Antarctic lichen Stereocaulon alpinum. Structures of the new compounds were elucidated by comprehensive analyses of 1D and 2D NMR and HREIMS experiments. Compound 3 exhibited cytotoxicity against HCT116 cells with the IC₅₀ value of 3.76 ± 0.03 μM and also inhibited NO production in LPS-induced RAW264.7 macrophages with the IC₅₀ value of 22.82 ± 0.015 μM. Full article

(This article belongs to the Topic Advances in Natural Products from Plants and Associated Microbes)

► Show Figures

Figure 1

15 pages, 1861 KiB

Open AccessArticle

Synthesis, Herbicidal Activity, Crop Safety and Soil Degradation of Pyrimidine- and Triazine-Substituted Chlorsulfuron Derivatives

by Lei Wu, Yu-Cheng Gu, Yong-Hong Li, Sha Zhou, Zhong-Wen Wang and Zheng-Ming Li

Molecules 2022, 27(7), 2362; https://doi.org/10.3390/molecules27072362 - 6 Apr 2022

Cited by 3 | Viewed by 2311

Abstract

Chlrosulfuron, a classical sulfonylurea herbicide that exhibits good safety for wheat but causes a certain degree of damage to subsequent corn in a wheat–corn rotation mode, has been suspended field application in China since 2014. Our previous study found that diethylamino-substituted chlorsulfuron derivatives [...] Read more.

Chlrosulfuron, a classical sulfonylurea herbicide that exhibits good safety for wheat but causes a certain degree of damage to subsequent corn in a wheat–corn rotation mode, has been suspended field application in China since 2014. Our previous study found that diethylamino-substituted chlorsulfuron derivatives accelerated the degradation rate in soil. In order to obtain sulfonylurea herbicides with good crop safety for both wheat and corn, while maintaining high herbicidal activities, a series of pyrimidine- and triazine-based diethylamino-substituted chlorsulfuron derivatives (W102–W111) were systematically evaluated. The structures of the synthesized compounds were confirmed with ¹H NMR, ¹³C NMR, and HRMS. The preliminary biological assay results indicate that the 4,6-disubstituted pyrimidine and triazine derivatives could maintain high herbicidal activity. It was found that the synthesized compounds could accelerate degradation rates, both in acidic and alkaline soil. Especially, in alkaline soil, the degradation rate of the target compounds accelerated more than 22-fold compared to chlorsulfuron. Moreover, most chlorsulfuron analogs exhibited good crop safety for both wheat and corn at high dosages. This study provided a reference for the further design of new sulfonylurea herbicides with high herbicidal activity, fast degradation rates, and high crop safety. Full article

► Show Figures

Figure 1

14 pages, 1035 KiB

Open AccessReview

Extracellular HSPs: The Potential Target for Human Disease Therapy

by Dong-Yi Li, Shan Liang, Jun-Hao Wen, Ji-Xin Tang, Shou-Long Deng and Yi-Xun Liu

Molecules 2022, 27(7), 2361; https://doi.org/10.3390/molecules27072361 - 6 Apr 2022

Cited by 17 | Viewed by 2704

Abstract

Heat shock proteins (HSPs) are highly conserved stress proteins known as molecular chaperones, which are considered to be cytoplasmic proteins with functions restricted to the intracellular compartment, such as the cytoplasm or cellular organelles. However, an increasing number of observations have shown that [...] Read more.

Heat shock proteins (HSPs) are highly conserved stress proteins known as molecular chaperones, which are considered to be cytoplasmic proteins with functions restricted to the intracellular compartment, such as the cytoplasm or cellular organelles. However, an increasing number of observations have shown that HSPs can also be released into the extracellular matrix and can play important roles in the modulation of inflammation and immune responses. Recent studies have demonstrated that extracellular HSPs (eHSPs) were involved in many human diseases, such as cancers, neurodegenerative diseases, and kidney diseases, which are all diseases that are closely linked to inflammation and immunity. In this review, we describe the types of eHSPs, discuss the mechanisms of eHSPs secretion, and then highlight their functions in the modulation of inflammation and immune responses. Finally, we take cancer as an example and discuss the possibility of targeting eHSPs for human disease therapy. A broader understanding of the function of eHSPs in development and progression of human disease is essential for developing new strategies to treat many human diseases that are critically related to inflammation and immunity. Full article

(This article belongs to the Special Issue Targeting Heat-Shock Proteins Machinery: An Update on the Discovery of New Drugs)

► Show Figures

Figure 1

15 pages, 3886 KiB

Open AccessArticle

The Root Extract of Peucedanum praeruptorum Dunn Exerts Anticancer Effects in Human Non-Small-Cell Lung Cancer Cells with Different EGFR Mutation Statuses by Suppressing MET Activity

by Hyun-Ji Park, Jae-Hoon Jeong and Shin-Hyung Park

Molecules 2022, 27(7), 2360; https://doi.org/10.3390/molecules27072360 - 6 Apr 2022

Cited by 8 | Viewed by 2562

Abstract

The aim of this study was to investigate the anticancer effects of the root extract of Peucedanum praeruptorum Dunn (EPP) in human non-small-cell lung cancer (NSCLC) cells and explore the mechanisms of action. We used four types of human lung cancer cell lines, [...] Read more.

The aim of this study was to investigate the anticancer effects of the root extract of Peucedanum praeruptorum Dunn (EPP) in human non-small-cell lung cancer (NSCLC) cells and explore the mechanisms of action. We used four types of human lung cancer cell lines, including H1299 (epidermal growth factor receptor (EGFR) wild-type), PC9 (EGFR Glu746-Ala750 deletion mutation in exon 19; EGFR tyrosine kinase inhibitor (TKI)-sensitive), H1975 (EGFR L858R/T790M double-mutant; EGFR TKI-resistant), and PC9/ER (erlotinib-resistant) cells. EPP suppressed cell growth and the colony formation of NSCLC cells in a concentration-dependent manner. EPP stimulated chromatin condensation, increased the percentage of sub-G1 phase cells, and enhanced the proportion of annexin V-positive cells, demonstrating that EPP triggered apoptosis in NSCLC cells regardless of the EGFR mutation and EGFR TKI resistance status. The phosphorylation level of the signal transducer and activator of transcription 3 (STAT3) and AKT was decreased by EPP. The expression of STAT3 target genes was also downregulated by EPP. EPP reversed hepatocyte growth factor (HGF)-induced MET phosphorylation and gefitinib resistance. Taken together, our results demonstrate that EPP exerted anticancer effects not only in EGFR TKI-sensitive NSCLC cells, but also in EGFR TKI-resistant NSCLC cells, by suppressing MET activity. Full article

(This article belongs to the Special Issue Plant Extracts: Biological and Pharmacological Activity—the Second Edition)

► Show Figures

Figure 1

15 pages, 1895 KiB

Open AccessArticle

Effects of Extraction Methods on Phenolic Content in the Young Bamboo Culm Extracts of Bambusa beecheyana Munro

by Mohd. Izuddin Nuzul, Vivien Yi Mian Jong, Lee Feng Koo, Thye Huat Chan, Chung Huap Ang, Juferi Idris, Rafidah Husen and Siaw Wei Wong

Molecules 2022, 27(7), 2359; https://doi.org/10.3390/molecules27072359 - 6 Apr 2022

Cited by 11 | Viewed by 3174

Abstract

Nowadays, many studies focus on the potential of bamboo as a source of bioactive compounds and natural antioxidants for nutraceutical, pharmaceutical, and food sources. This study is a pioneering effort to determine the total phenolic content, total flavonoid content and free radical scavenging [...] Read more.

Nowadays, many studies focus on the potential of bamboo as a source of bioactive compounds and natural antioxidants for nutraceutical, pharmaceutical, and food sources. This study is a pioneering effort to determine the total phenolic content, total flavonoid content and free radical scavenging activity, as well as the phenolic identification and quantification of Bambusa beecheyana. The study was conducted by using ethanol, methanol, and water for solvent extraction by applying cold maceration, Soxhlet, and ultrasonic-assisted extraction techniques. The results showed that Soxhlet and ultrasonic-assisted Bambusa beecheyana culm extracts had an increase in the extract’s dry yield (1.13–8.81%) but a constant p-coumaric acid (4) content (0.00035 mg/g) as compared to the extracts from the cold maceration. The ultrasonic-assisted extraction method required only a small amount (250 mL) of solvent to extract the bamboo culms. A significant amount of total phenolics (107.65 ± 0.01 mg GAE/g) and flavonoids (43.89 ± 0.05 mg QE/g) were found in the Soxhlet methanol culm extract. The extract also possessed the most potent antioxidant activity with an IC₅₀ value of 40.43 µg/mL as compared to the positive control, ascorbic acid. The UHPLC–ESI–MS/MS analysis was carried out on the Soxhlet methanol extract, ultrasonic-assisted extract at 40 min, and cold methanol extract. The analysis resulted in the putative identification of a total of five phenolics containing cinnamic acid derivatives. The two cinnamic acid derivatives, p-coumaric acid (4) and 4-methoxycinnamic acid (5), were then used as markers to quantify the concentration of both compounds in all the extracts. Both compounds were not found in the water extracts. These results revealed that the extract from Soxhlet methanol of Bambusa beecheyana could be a potential botanical source of natural antioxidants. This study provides an important chemical composition database for further preclinical research on Bambusa beecheyana. Full article

► Show Figures

Figure 1

16 pages, 2298 KiB

Open AccessArticle

Hydrophobicity Enhances the Formation of Protein-Stabilized Foams

by Roy J. B. M. Delahaije and Peter A. Wierenga

Molecules 2022, 27(7), 2358; https://doi.org/10.3390/molecules27072358 - 6 Apr 2022

Cited by 12 | Viewed by 2777

Abstract

Screening proteins for their potential use in foam applications is very laborious and time consuming. It would be beneficial if the foam properties could be predicted based on their molecular properties, but this is currently not possible. For protein-stabilized emulsions, a model was [...] Read more.

Screening proteins for their potential use in foam applications is very laborious and time consuming. It would be beneficial if the foam properties could be predicted based on their molecular properties, but this is currently not possible. For protein-stabilized emulsions, a model was recently introduced to predict the emulsion properties from the protein molecular properties. Since the fundamental mechanisms for foam and emulsion formation are very similar, it is of interest to determine whether the link to molecular properties defined in that model is also applicable to foams. This study aims to link the exposed hydrophobicity with the foam ability and foam stability, using lysozyme variants with altered hydrophobicity, obtained from controlled heat treatment (77 °C for 0–120 min). To establish this link, the molecular characteristics, interfacial properties, and foam ability and stability (at different concentrations) were analysed. The increasing hydrophobicity resulted in an increased adsorption rate constant, and for concentrations in the protein-poor regime, the increasing hydrophobicity enhanced foam ability (i.e., interfacial area created). At higher relative exposed hydrophobicity (i.e., ~2–5 times higher than native lysozyme), the adsorption rate constant and foam ability became independent of hydrophobicity. The foam stability (i.e., foam collapse) was affected by the initial foam structure. In the protein-rich regime—with nearly identical foam structure—the hydrophobicity did not affect the foam stability. The link between exposed hydrophobicity and foam ability confirms the similarity between protein-stabilized foams and emulsions, and thereby indicates that the model proposed for emulsions can be used to predict foam properties in the future. Full article

(This article belongs to the Special Issue Chemical and Functional Properties of Food Proteins)

► Show Figures

Figure 1

15 pages, 4824 KiB

Open AccessArticle

Hydrogenation of β-Keto Sulfones to β-Hydroxy Sulfones with Alkyl Aluminum Compounds: Structure of Intermediate Hydroalumination Products

by Michał Kotecki, Zbigniew Ochal, Paweł Socha, Vadim Szejko, Łukasz Dobrzycki, Mariola Stypik and Wanda Ziemkowska

Molecules 2022, 27(7), 2357; https://doi.org/10.3390/molecules27072357 - 6 Apr 2022

Cited by 2 | Viewed by 2204

Abstract

β-Hydroxy sulfones are important in organic synthesis. The simplest method of β-hydroxy sulfones synthesis is the hydrogenation of β-keto sulfones. Herein, we report the reducing properties of alkyl aluminum compounds R₃Al (R = Et, i-Bu, n-Bu, t-Bu and [...] Read more.

β-Hydroxy sulfones are important in organic synthesis. The simplest method of β-hydroxy sulfones synthesis is the hydrogenation of β-keto sulfones. Herein, we report the reducing properties of alkyl aluminum compounds R₃Al (R = Et, i-Bu, n-Bu, t-Bu and n-Hex); i-Bu₂AlH; Et₂AlCl and EtAlCl₂ in the hydrogenation of β-keto sulfones. The compounds i-Bu₂AlH, i-Bu₃Al and Et₃Al are the at best reducing agents of β-keto sulfones to β-hydroxy sulfones. In reactions of β-keto sulfones with aluminum trialkyls, hydroalumination products with β-hydroxy sulfone ligands [R₂AlOC(C₆H₅)CH₂S(O)₂(p-R¹C₆H₄]_n [where n = 1,2; 2aa: R = i-Bu, R¹ = CH₃; 2ab: R = i-Bu, R¹ = Cl; 2ba: R = Et, R¹ = CH₃; 2bb: R = Et, R¹ = Cl] and {[Et₂AlOC(C₆H₅)CH₂S(O)₂(p-ClC₆H₄]∙Et₃Al}_n3bb were obtained. These complexes in the solid state have a dimeric structure, while in solutions, they appear as equilibrium monomer–dimer mixtures. The hydrolysis of both the isolated 2aa, 2ab, 2ba, 2bb and 3bb and the postreaction mixtures quantitatively leads to pure racemic β-hydroxy sulfones. Hydroalumination reaction of β-keto sulfones with alkyl aluminum compounds and subsequent hydrolysis of the complexes is a simple and very efficient method of β-hydroxy sulfones synthesis. Full article

► Show Figures

Graphical abstract

12 pages, 2683 KiB

Open AccessArticle

Integration of Metal-Organic Frameworks with Bi-Nanoprobes as Dual-Emissive Ratiometric Sensors for Fast and Highly Sensitive Determination of Food Hazards

by Chi-Xuan Yao, Lu Dong, Lu Yang, Jin Wang, Shi-Jie Li, Huan Lv, Xue-Meng Ji, Jing-Min Liu and Shuo Wang

Molecules 2022, 27(7), 2356; https://doi.org/10.3390/molecules27072356 - 6 Apr 2022

Cited by 8 | Viewed by 2367

Abstract

Functional nanoprobes which detect specific food hazards quickly and simply are still in high demand in the field of food-safety inspection research. In the present work, a dual-emission metal-organic framework-based ratiometric fluorescence probe was integrated to detect Cu²⁺ and Pb²⁺ with [...] Read more.

Functional nanoprobes which detect specific food hazards quickly and simply are still in high demand in the field of food-safety inspection research. In the present work, a dual-emission metal-organic framework-based ratiometric fluorescence probe was integrated to detect Cu²⁺ and Pb²⁺ with rapidness and ease. Specifically, quantum dots (QDs) and carbon quantum dots (CQDs) were successfully embedded into zeolitic imidazolate framework-67 (ZIF-67) to function as a novel ratiometric fluorescent sensing composite. The ratiometric fluorescence signal of CQDs/QDs@ZIF-67 was significantly aligned with the concentration of metal ions to give an extremely low detection limit of 0.3324 nM. The highly sensitive and selective CQDs/QDs@ZIF-67 composite showed potential for the rapid and cost-effective detection of two metal ions. Full article

► Show Figures

Figure 1

18 pages, 3592 KiB

Open AccessArticle

Elucidation of Analytical–Compositional Fingerprinting of Three Different Species of Chili Pepper by Using Headspace Solid-Phase Microextraction Coupled with Gas Chromatography–Mass Spectrometry Analysis, and Sensory Profile Evaluation

by Emanuela Trovato, Federica Vento, Donato Creti, Paola Dugo and Luigi Mondello

Molecules 2022, 27(7), 2355; https://doi.org/10.3390/molecules27072355 - 6 Apr 2022

Cited by 16 | Viewed by 3193

Abstract

The aim of the present study was to determine the volatile compounds of three different species of chili peppers, using solid-phase microextraction (SPME) methods in combination with gas chromatography–mass spectrometry (GC-MS). The detection of marker aroma compounds could be used as a parameter [...] Read more.

The aim of the present study was to determine the volatile compounds of three different species of chili peppers, using solid-phase microextraction (SPME) methods in combination with gas chromatography–mass spectrometry (GC-MS). The detection of marker aroma compounds could be used as a parameter to differentiate between species of chili peppers for their detection and traceability in chili pepper food. The sensorial contribution was also investigated to identify the predominant notes in each species and to evaluate how they can influence the overall aroma. Three different pepper species belonging to the Capsicum genus were analyzed: Chinense, Annuum, and Baccatum. A total of 269 volatile compounds were identified in these species of chili peppers. The Capsicum annum species were characterized by a high number of acids and ketones, while the Capsicum chinense and Capsicum baccatum were characterized by esters and aldehydes, respectively. The volatile profile of extra virgin olive oils (EVOOs) flavored with chili peppers was also investigated, and principal component analysis (PCA) and hierarchical cluster analysis (HCA) of the volatile profiles were demonstrated to be a powerful analytical strategy for building a model that highlights the potential of a volatile characterization approach for use in evaluating food traceability and authenticity. Full article

(This article belongs to the Special Issue Food Chemistry: A Fascinating World. A Themed Issue in Honor of Professor Giovanni Dugo on the Occasion of His 80th Birthday)

► Show Figures

Figure 1

19 pages, 4169 KiB

Open AccessArticle

Amphipolar, Amphiphilic 2,4-diarylpyrano[2,3-b]indoles as Turn-ON Luminophores in Acidic and Basic Media

by Tobias Wilcke, Alexandru Postole, Marcel Krüsmann, Matthias Karg and Thomas J. J. Müller

Molecules 2022, 27(7), 2354; https://doi.org/10.3390/molecules27072354 - 6 Apr 2022

Cited by 1 | Viewed by 2380

Abstract

A versatile amphiphilic pyrano[2,3-b]indole for halochromic turn-ON luminescence in acidic or basic media is accessed by an insertion-coupling-cycloisomerization and adjusting solubilizing and phenolic functionalities. While almost non-emissive in neutral solutions, treatment with acids or bases like trifluoroacetic acid (TFA) or 1,8-diazabicyclo[5.4.0]undec-7-ene [...] Read more.

A versatile amphiphilic pyrano[2,3-b]indole for halochromic turn-ON luminescence in acidic or basic media is accessed by an insertion-coupling-cycloisomerization and adjusting solubilizing and phenolic functionalities. While almost non-emissive in neutral solutions, treatment with acids or bases like trifluoroacetic acid (TFA) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) reveals distinct luminescence at wavelengths of 540 nm or 630 nm in propan-2-ol, respectively. Turn-ON emission can be detected at pH values as mild as pH = 5.31 or 8.70. Quantum yields in propan-2-ol are substantial for protonated (Φ_f = 0.058) and deprotonated (Φ_f = 0.059) species. Photometrically, pK_a₁ of 3.5 and pK_a₂ of 10.5 were determined in propan-2-ol. With lipophilic polyether sidechains and hydrophilic protonation and deprotonation sites the molecule can be regarded as amphipolar, which results in good solubility properties for different organic solvents. In aqueous media, an organic co-solvent like propan-2-ol (35%) or tetrahydrofuran (25%) is needed, and the solution can be diluted with pure water without precipitation of the compound. At higher concentrations of water, a turbid solution is formed, which indicates the formation of micellar structures or clusters. With dynamic light scattering we could show that these clusters increase in size with increasing water content. Full article

(This article belongs to the Special Issue Novel Fluorophores and Their Applications)

► Show Figures

Graphical abstract

14 pages, 4447 KiB

Open AccessArticle

Smart Titanium Wire Used for the Evaluation of Hydrophobic/Hydrophilic Interaction by In-Tube Solid Phase Microextraction

by Yuping Zhang, Ning Wang, Zhenyu Lu, Na Chen, Chengxing Cui and Xinxin Chen

Molecules 2022, 27(7), 2353; https://doi.org/10.3390/molecules27072353 - 6 Apr 2022

Cited by 8 | Viewed by 1988

Abstract

Evaluation of the hydrophobic/hydrophilic interaction individually between the sorbent and target compounds in sample pretreatment is a big challenge. Herein, a smart titanium substrate with switchable surface wettability was fabricated and selected as the sorbent for the solution. The titanium wires and meshes [...] Read more.

Evaluation of the hydrophobic/hydrophilic interaction individually between the sorbent and target compounds in sample pretreatment is a big challenge. Herein, a smart titanium substrate with switchable surface wettability was fabricated and selected as the sorbent for the solution. The titanium wires and meshes were fabricated by simple hydrothermal etching and chemical modification so as to construct the superhydrophilic and superhydrophobic surfaces. The micro/nano hierarchical structures of the formed TiO₂ nanoparticles in situ on the surface of Ti substrates exhibited the switchable surface wettability. After UV irradiation for about 15.5 h, the superhydrophobic substrates became superhydrophilic. The morphologies and element composition of the wires were observed by SEM, EDS, and XRD, and their surface wettabilities were measured using the Ti mesh by contact angle goniometer. The pristine hydrophilic wire, the resulting superhydrophilic wire, superhydrophobic wire, and the UV-irradiated superhydrophilic wire were filled into a stainless tube as the sorbent instead of the sample loop of a six-port valve for on-line in-tube solid-phase microextraction. When employed in conjunction with HPLC, four kinds of wires were comparatively applied to extract six estrogens in water samples. The optimal conditions for the preconcentration and separation of target compounds were obtained with a sample volume of 60 mL, an injection rate of 2 mL/min, a desorption time of 2 min, and a mobile phase of acetonile/water (47/53, v/v). The results showed that both the superhydrophilic wire and UV-irradiated wire had the highest extraction efficiency for the polar compounds of estrogens with the enrichment factors in the range of 20–177, while the superhydrophobic wire exhibited the highest extraction efficiency for the non-polar compounds of five polycyclic aromatic hydrocarbons (PAHs). They demonstrated that extraction efficiency was mainly dependent on the surface wettability of the sorbent and the polarity of the target compounds, which was in accordance with the molecular theory of like dissolves like. Full article

(This article belongs to the Special Issue Solid-Phase Microextraction and Related Techniques in Bioanalysis)

► Show Figures

Figure 1

12 pages, 2397 KiB

Open AccessArticle

On the Nature of Extra-Framework Aluminum Species and Improved Catalytic Properties in Steamed Zeolites

by Konstantin Khivantsev, Nicholas R. Jaegers, Libor Kovarik, Miroslaw A. Derewinski, Ja-Hun Kwak and Janos Szanyi

Molecules 2022, 27(7), 2352; https://doi.org/10.3390/molecules27072352 - 6 Apr 2022

Cited by 14 | Viewed by 4784

Abstract

Steamed zeolites exhibit improved catalytic properties for hydrocarbon activation (alkane cracking and dehydrogenation). The nature of this practically important phenomenon has remained a mystery for the last six decades and was suggested to be related to the increased strength of zeolitic Bronsted acid [...] Read more.

Steamed zeolites exhibit improved catalytic properties for hydrocarbon activation (alkane cracking and dehydrogenation). The nature of this practically important phenomenon has remained a mystery for the last six decades and was suggested to be related to the increased strength of zeolitic Bronsted acid sites after dealumination. We now utilize state-of-the-art infrared spectroscopy measurements and prove that during steaming, aluminum oxide clusters evolve (due to hydrolysis of Al out of framework positions with the following clustering) in the zeolitic micropores with properties very similar to (nano) facets of hydroxylated transition alumina surfaces. The Bronsted acidity of the zeolite does not increase and the total number of Bronsted acid sites decreases during steaming. O₅Al(VI)-OH surface sites of alumina clusters dehydroxylate at elevated temperatures to form penta-coordinate Al₁O₅ sites that are capable of initiating alkane cracking by breaking the first C-H bond very effectively with much lower barriers (at lower temperatures) than for protolytic C-H bond activation, with the following reaction steps catalyzed by nearby zeolitic Bronsted acid sites. This explains the underlying mechanism behind the improved alkane cracking and alkane dehydrogenation activity of steamed zeolites: heterolytic C-H bond breaking occurs on Al-O sites of aluminum oxide clusters confined in zeolitic pores. Our findings explain the origin of enhanced activity of steamed zeolites at the molecular level and provide the missing understanding of the nature of extra-framework Al species formed in steamed/dealuminated zeolites. Full article

(This article belongs to the Special Issue Composite Porous Materials in Catalysis)

► Show Figures

Figure 1

44 pages, 5686 KiB

Open AccessFeature PaperReview

Bioactive Compounds from Terrestrial and Marine-Derived Fungi of the Genus Neosartorya †

by Joana D. M. de Sá, Decha Kumla, Tida Dethoup and Anake Kijjoa

Molecules 2022, 27(7), 2351; https://doi.org/10.3390/molecules27072351 - 6 Apr 2022

Cited by 11 | Viewed by 3765

Abstract

Fungi comprise the second most species-rich organism group after that of insects. Recent estimates hypothesized that the currently reported fungal species range from 3.5 to 5.1 million types worldwide. Fungi can grow in a wide range of habitats, from the desert to the [...] Read more.

Fungi comprise the second most species-rich organism group after that of insects. Recent estimates hypothesized that the currently reported fungal species range from 3.5 to 5.1 million types worldwide. Fungi can grow in a wide range of habitats, from the desert to the depths of the sea. Most develop in terrestrial environments, but several species live only in aquatic habitats, and some live in symbiotic relationships with plants, animals, or other fungi. Fungi have been proved to be a rich source of biologically active natural products, some of which are clinically important drugs such as the β-lactam antibiotics, penicillin and cephalosporin, the immunosuppressant, cyclosporine, and the cholesterol-lowering drugs, compactin and lovastatin. Given the estimates of fungal biodiversity, it is easy to perceive that only a small fraction of fungi worldwide have ever been investigated regarding the production of biologically valuable compounds. Traditionally, fungi are classified primarily based on the structures associated with sexual reproduction. Thus, the genus Neosartorya (Family Trichocomaceae) is the telemorphic (sexual state) of the Aspergillus section known as Fumigati, which produces both a sexual state with ascospores and an asexual state with conidiospores, while the Aspergillus species produces only conidiospores. However, according to the Melbourne Code of nomenclature, only the genus name Aspergillus is to be used for both sexual and asexual states. Consequently, the genus name Neosartorya was no longer to be used after 1 January 2013. Nevertheless, the genus name Neosartorya is still used for the fungi that had already been taxonomically classified before the new rule was in force. Another aspect is that despite the small number of species (23 species) in the genus Neosartorya, and although less than half of them have been investigated chemically, the chemical diversity of this genus is impressive. Many chemical classes of compounds, some of which have unique scaffolds, such as indole alkaloids, peptides, meroterpenes, and polyketides, have been reported from its terrestrial, marine-derived, and endophytic species. Though the biological and pharmacological activities of a small fraction of the isolated metabolites have been investigated due to the available assay systems, they exhibited relevant biological and pharmacological activities, such as anticancer, antibacterial, antiplasmodial, lipid-lowering, and enzyme-inhibitory activities. Full article

(This article belongs to the Special Issue Microbial Natural Products 2022)

► Show Figures

Figure 1

21 pages, 2760 KiB

Open AccessArticle

Non-Peptide Opioids Differ in Effects on Mu-Opioid (MOP) and Serotonin 1A (5-HT_1A) Receptors Heterodimerization and Cellular Effectors (Ca²⁺, ERK1/2 and p38) Activation

by Vlad Radoi, Gerd Jakobsson, Vinko Palada, Andrej Nikosjkov, Henrik Druid, Lars Terenius, Eva Kosek and Vladana Vukojević

Molecules 2022, 27(7), 2350; https://doi.org/10.3390/molecules27072350 - 6 Apr 2022

Cited by 3 | Viewed by 4000

Abstract

The importance of the dynamic interplay between the opioid and the serotonin neuromodulatory systems in chronic pain is well recognized. In this study, we investigated whether these two signalling pathways can be integrated at the single-cell level via direct interactions between the mu-opioid [...] Read more.

The importance of the dynamic interplay between the opioid and the serotonin neuromodulatory systems in chronic pain is well recognized. In this study, we investigated whether these two signalling pathways can be integrated at the single-cell level via direct interactions between the mu-opioid (MOP) and the serotonin 1A (5-HT_1A) receptors. Using fluorescence cross-correlation spectroscopy (FCCS), a quantitative method with single-molecule sensitivity, we characterized in live cells MOP and 5-HT_1A interactions and the effects of prolonged (18 h) exposure to selected non-peptide opioids: morphine, codeine, oxycodone and fentanyl, on the extent of these interactions. The results indicate that in the plasma membrane, MOP and 5-HT_1A receptors form heterodimers that are characterized with an apparent dissociation constant

K_{d}^{app}

= (440 ± 70) nM). Prolonged exposure to all non-peptide opioids tested facilitated MOP and 5-HT_1A heterodimerization and stabilized the heterodimer complexes, albeit to a different extent:

K_{d, Fentanyl}^{app}

= (80 ± 70) nM),

K_{d, Morphine}^{app}

= (200 ± 70) nM,

K_{d, Codeine}^{app}

= (100 ± 70) nM and

K_{d, Oxycodone}^{app}

= (200 ± 70) nM. The non-peptide opioids differed also in the extent to which they affected the mitogen-activated protein kinases (MAPKs) p38 and the extracellular signal-regulated kinase (Erk1/2), with morphine, codeine and fentanyl activating both pathways, whereas oxycodone activated p38 but not ERK1/2. Acute stimulation with different non-peptide opioids differently affected the intracellular Ca²⁺ levels and signalling dynamics. Hypothetically, targeting MOP–5-HT_1A heterodimer formation could become a new strategy to counteract opioid induced hyperalgesia and help to preserve the analgesic effects of opioids in chronic pain. Full article

(This article belongs to the Special Issue Opioids and Their Receptors: Present and Emerging Concepts in Opioid Drug Discovery II)

► Show Figures

Figure 1

12 pages, 1921 KiB

Open AccessArticle

Levonorgestrel Microneedle Array Patch for Sustained Release Contraception: Formulation, Optimization and In Vivo Characterization

by Amarjitsing Rajput, Riyaz Ali M. Osmani, Achyut Khire, Sanket Jaiswal and Rinti Banerjee

Molecules 2022, 27(7), 2349; https://doi.org/10.3390/molecules27072349 - 6 Apr 2022

Cited by 13 | Viewed by 4127

Abstract

Background: The goal of this work was to develop a levonorgestrel liposome-loaded microneedle array patch for contraception. Methods: Levonorgestrel-loaded liposome was formulated by a solvent injection technique, characterized, and studied. Results: The formulated liposomes were characterized for particle size (147 ± 8 nm), [...] Read more.

Background: The goal of this work was to develop a levonorgestrel liposome-loaded microneedle array patch for contraception. Methods: Levonorgestrel-loaded liposome was formulated by a solvent injection technique, characterized, and studied. Results: The formulated liposomes were characterized for particle size (147 ± 8 nm), polydispersity index (0.207 ± 0.03), zeta potential (−23 ± 4.25 mV), drug loading (18 ± 3.22%) and entrapment efficiency (85 ± 4.34%). A cryo high-resolution transmission electron microscopy and cryo field emission gun scanning electron microscopy study showed spherical shaped particles with a smooth surface. The in vitro drug release and in vivo pharmacokinetic study showed sustained behaviour of Levonorgestrel for 28 days. Conclusion: The levonorgestrel liposome-loaded microneedle array patch showed better contraception than the drug-loaded microneedle array patch. Full article

(This article belongs to the Special Issue Nanomedicine Based Drug Delivery Systems: Recent Developments and Future Prospects)

► Show Figures

Graphical abstract

12 pages, 2587 KiB

Open AccessArticle

Effect of Natural Deep Eutectic Solvents on trans-Resveratrol Photo-Chemical Induced Isomerization and 2,4,6-Trihydroxyphenanthrene Electro-Cyclic Formation

by Roberto Mattioli, Daniel Di Risola, Rodolfo Federico, Alessia Ciogli, Francesco Gasparrini, Claudio Villani, Mario Fontana, Anna Maggiore, Maria d’Erme, Luciana Mosca and Antonio Francioso

Molecules 2022, 27(7), 2348; https://doi.org/10.3390/molecules27072348 - 6 Apr 2022

Cited by 8 | Viewed by 2764

Abstract

trans-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans/cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a [...] Read more.

trans-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans/cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a potentially harmful compound which can exert genotoxic effects. In this work we improved the chromatographic separation and determination of the two resveratrol isomers and of THP by using a non-commercial pentafluorophenyl stationary phase. We assessed the effect of natural deep eutectic solvents (NaDES) as possible photo-protective agents by evaluating cis-resveratrol isomer and THP formation under different UV-light exposure conditions with the aim of enhancing resveratrol photostability and inhibiting THP production. Our results demonstrate a marked photoprotective effect exerted by glycerol-containing NaDES, and in particular by proline/glycerol NaDES, which exerts a strong inhibitory effect on the photochemical isomerization of resveratrol and significantly limits the formation of the toxic derivative THP. Considering the presence of resveratrol in various commercial products, these results are of note in view of the potential genotoxic risk associated with its photochemical degradation products and in view of the need for the development of green, eco-sustainable and biocompatible resveratrol photo-stable formulations. Full article

(This article belongs to the Special Issue Resveratrol News & Views: From the Molecular Mechanism to Nutritional and Biomedical Applications)

► Show Figures

Figure 1

10 pages, 3694 KiB

Open AccessArticle

Phosphorylation of cPLA₂α at Ser⁵⁰⁵ Is Necessary for Its Translocation to PtdInsP₂-Enriched Membranes

by Javier Casas, Jesús Balsinde and María A. Balboa

Molecules 2022, 27(7), 2347; https://doi.org/10.3390/molecules27072347 - 6 Apr 2022

Cited by 3 | Viewed by 1803

Abstract

Group IVA cytosolic phospholipase A₂α (cPLA₂α) is a key enzyme in physiology and pathophysiology because it constitutes a rate-limiting step in the pathway for the generation of pro- and anti-inflammatory eicosanoid lipid mediators. cPLA₂α activity is tightly [...] Read more.

Group IVA cytosolic phospholipase A₂α (cPLA₂α) is a key enzyme in physiology and pathophysiology because it constitutes a rate-limiting step in the pathway for the generation of pro- and anti-inflammatory eicosanoid lipid mediators. cPLA₂α activity is tightly regulated by multiple factors, including the intracellular Ca²⁺ concentration, phosphorylation reactions, and cellular phosphatidylinositol (4,5) bisphosphate levels (PtdInsP₂). In the present work, we demonstrate that phosphorylation of the enzyme at Ser⁵⁰⁵ is an important step for the translocation of the enzyme to PtdInsP₂–enriched membranes in human cells. Constructs of eGFP-cPLA₂ mutated in Ser⁵⁰⁵ to Ala (S505A) exhibit a delayed translocation in response to elevated intracellular Ca²⁺, and also in response to increases in intracellular PtdInsP₂ levels. Conversely, translocation of a phosphorylation mimic mutant (S505E) is fully observed in response to cellular increases in PtdInsP₂ levels. Collectively, these results suggest that phosphorylation of cPLA₂α at Ser⁵⁰⁵ is necessary for the enzyme to translocate to internal membranes and mobilize arachidonic acid for eicosanoid synthesis. Full article

(This article belongs to the Special Issue Lipids–Lipolytic Enzymes–Lipid Analysis: A Themed Issue Dedicated to Prof. Edward A. Dennis for His 80th Birthday)

► Show Figures

Figure 1

23 pages, 4945 KiB

Open AccessArticle

Computational Analysis and Biological Activities of Oxyresveratrol Analogues, the Putative Cyclooxygenase-2 Inhibitors

by Nathjanan Jongkon, Boonwiset Seaho, Ngampuk Tayana, Saisuree Prateeptongkum, Nongnaphat Duangdee and Panichakorn Jaiyong

Molecules 2022, 27(7), 2346; https://doi.org/10.3390/molecules27072346 - 6 Apr 2022

Cited by 6 | Viewed by 3141

Abstract

Polyphenols are a large family of naturally occurring phytochemicals. Herein, oxyresveratrol was isolated from ethanolic crude extracts of Artocarpus lacucha Buch.-Ham., and chemically modified to derive its lipophilic analogues. Biological screening assays showed their inhibitory potency against cyclooxygenase-2 (COX-2) with very low cytotoxicity [...] Read more.

Polyphenols are a large family of naturally occurring phytochemicals. Herein, oxyresveratrol was isolated from ethanolic crude extracts of Artocarpus lacucha Buch.-Ham., and chemically modified to derive its lipophilic analogues. Biological screening assays showed their inhibitory potency against cyclooxygenase-2 (COX-2) with very low cytotoxicity to the MRC-5 normal cell lines. At the catalytic site of COX-2, docking protocols with ChemPLP, GoldScore and AutoDock scoring functions were carried out to reveal hydrogen bonding interactions with key polar contacts and hydrophobic pi-interactions. For more accurate binding energetics, COX-2/ligand complexes at the binding region were computed in vacuo and implicit aqueous solvation using M06-2X density functional with 6-31G+(d,p) basis set. Our computational results confirmed that dihydrooxyresveratrol (4) is the putative inhibitor of human COX-2 with the highest inhibitory activity (IC₅₀ of 11.50 ± 1.54 µM) among studied non-fluorinated analogues for further lead optimization. Selective substitution of fluorine provides a stronger binding affinity; however, lowering the cytotoxicity of a fluorinated analogue to a normal cell is challenging. The consensus among biological activities, ChemPLP docking score and the binding energies computed at the quantum mechanical level is obviously helpful for identification of oxyresveratrol analogues as a putative anti-inflammatory agent. Full article

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Molecules, Volume 27, Issue 7 (April-1 2022) – 340 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI