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1.
Bioorg Chem ; 151: 107688, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39106712

ABSTRACT

Ergosterol peroxide (EP) isolated from the edible medicinal fungus Pleurotus ferulae has a wide range of anti-tumor activity, but poor water solubility and low bioavailability limit further application. In this study, EP was structurally modified using triphenylphosphine (TPP+), which combines mitochondrial targeting, amphiphilicity, and cytotoxicity. A series of TPP+-conjugated ergosterol peroxide derivatives (TEn) with different length linker arms were synthesized. The structure-activity relationship showed that the anticancer activity of TEn gradually decreased with the elongation of the linker arm. The compound TE3 has the optimal and broadest spectrum of antitumor effects. It mainly through targeting mitochondria, inducing ROS production, disrupting mitochondrial function, and activating mitochondria apoptosis pathway to exert anti-cervical cancer activity. Among them, TPP+ only acted as a mitochondrial targeting group, while EP containing peroxide bridge structure served as an active group to induce ROS. In vivo experiments have shown that TE3 has better anti-cervical cancer activity and safety than the first-line anticancer drug cisplatin, and can activate the immune response in mice. Although TE3 exhibits some acute toxicity, it is not significant at therapeutic doses. Therefore, TE3 has the potential for further development as an anti-cervical cancer drug.

2.
Food Chem ; 460(Pt 1): 140540, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39053274

ABSTRACT

In recent years, red wine drinking has become more popular in China owing to its antioxidant effects. However, the key antioxidant compounds and their action mechanisms of Chinese red wines are still unclear. Herein, the antioxidant activities and chemical compositions of 45 Chinese Cabernet Sauvignon red wine samples were determined using chemical antioxidant assays and an UHPLC-QTOF-MS-based untargeted metabolomics method. The key antioxidant compounds in red wines and potential action mechanisms were revealed by integrating network pharmacology and molecular docking approaches. Results showed that there are 8 key antioxidant compounds in the red wine samples. These compounds are involved in several metabolic pathways in the body, particularly PI3K/AKT. What's more, they bind to the core antioxidant targets through hydrogen bonding and hydrophobic interaction. Among them, myricetin, laricitrin, 2,3,8-tri-O-methylellagic acid and AKT1 have the highest binding energies. This study could provide the theoretical basis for further investigation of physiological activities and functions of Chinese red wines.

3.
Int J Biol Macromol ; 277(Pt 2): 134321, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39084423

ABSTRACT

Chitosan, a versatile amino polysaccharide biopolymer derived from chitin, exhibits broad-spectrum antimicrobial activity against various pathogenic microorganisms, including gram-negative and gram-positive bacteria, as well as fungi. Due to its ubiquitous use in medications, food, cosmetics, chemicals, and crops, it is an effective antibacterial agent. However, the antimicrobial performance of chitosan is influenced by multiple factors, which have been extensively investigated and reported in the literature. The goal of this review paper is to present a thorough grasp of the mechanisms of action and determining variables of chitosan and its derivatives' antibacterial activity. The article begins by providing a brief background on chitosan and its antimicrobial properties, followed by the importance of understanding the mechanism of action and factors influencing its activity".

4.
Zhonghua Nan Ke Xue ; 30(1): 51-59, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-39046414

ABSTRACT

OBJECTIVE: To analyze the main active components and potential molecular mechanism of Yishen Tongluo Prescription (YTP) in the treatment of male infertility based on network pharmacological technology. METHODS: We searched and sorted the main active components of YTP and their individual potential targets in the databases of Systematic Pharmacology of Traditional Chinese Medicine (TCM) and Bioinformatics Analysis Tool of the Molecular Mechanism of TCM, and screened the targets related to male infertility diseases in the databases of Genecards, DisGeNET and OMIM. We made a Venn diagram by intersecting the predicted targets of YTP and those of male infertility diseases, constructed visualized networks for the association of the intersection targets and protein-protein interaction (PPI) using the Cytoscape software and STRING platform respectively, and conducted gene ontology (GO) and KEGG enrichment analyses using the DAVID database and R language "Cluster Profiler" software package respectively. RESULTS: A total of 99 active components, 250 targets of YTP, 4 397 targets of male infertility and 127 common targets were identified. GO analysis revealed that the biological processes of the common targets mainly included transcriptional regulation of RNA polymerase promoter Ⅱ, regulation of gene expressions, regulation of apoptosis, responses to estrogen, and cell responses to hypoxia. KEGG analysis showed significant enrichment of the common targets in the estrogen signaling pathway, cell apoptosis pathway, AGE-RAGE signaling pathway in diabetic complications, and TNF signaling pathway. CONCLUSION: Through network pharmacology, we identified the main active components of YTP and its multi-target and multi-pathway mechanism in the treatment of male infertility, which has paved the ground for animal and cell experiments in verifying the action mechanism of YTP on male infertility.


Subject(s)
Drugs, Chinese Herbal , Infertility, Male , Network Pharmacology , Male , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Infertility, Male/drug therapy , Humans , Protein Interaction Maps , Medicine, Chinese Traditional/methods , Computational Biology , Gene Ontology , Apoptosis/drug effects
5.
Mol Divers ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926303

ABSTRACT

Succinate dehydrogenase inhibitors (SDHIs) as one of the fastest-growing fungicide categories for plant protection. In this study, a series of N'-phenyl pyridylcarbohydrazides as analogues of commercial SDHIs were designed and evaluated for inhibition activity on phytopathogenic fungi to search for potential novel SDHIs. The determination of antifungal activity in vitro and in vivo led to the discovery of a series of compounds with high activity and broad-spectrum property. Especially, N'-(4-fluorophenyl)picolinohydrazide (1c) and N'-(3,4-fluorophenyl)picolinohydrazide (1ae) showed 0.041-1.851 µg/mL of EC50 values on twelve fungi, superior to positive controls carbendazim and boscalid. In vivo activity, 1c at 50 µg/mL showed 61% of control efficacy at the post-treatment 9th day for the infection of P. piricola on apples, slightly smaller than 70% of carbendazim. In terms of action mechanism, 1c showed strong inhibition activity with IC50 of 0.107 µg/mL on SDH in Alternaria brassicae, superior to positive SDHI boscalid (IC50 0.182 µg/mL). Molecular docking indicated that 1c can well bind with the ubiquinone-binding region of SDH mainly by hydrogen bond, carbon hydrogen bond, π-alkyl, amide-π stacking, F-N and F-H interactions. Furthermore, scanning and transmission electron micrographs showed that 1c was able to obviously change the structure of mycelia and cell membrane. Fluorescence staining analysis showed that 1c could increase both the intracellular reactive oxygen species level and mitochondrial membrane potential. Finally, seed germination test, seedling growth test and cytotoxicity assay showed that 1c had very low toxicity to plant growth and mammalian cells. Thus, N'-phenyl pyridylcarbohydrazides especially 1c and 1ae can be considered promising fungicide alternatives for plant protection.

6.
ChemSusChem ; : e202400660, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847086

ABSTRACT

The two-electron electrocatalytic oxygen reduction reaction (ORR) to hydrogen peroxide (H2O2) is a valuable alternative to the more conventional and energy-intensive anthraquinone process. From a circularity viewpoint, metal-free catalysts constitute a sustainable alternative for the process. In particular, lightweight hetero-doped C-materials are cost-effective and easily scalable samples that replace - more and more frequently - the use of critical raw elements in the preparation of highly performing (electro)catalysts. Anyhow, their large-scale exploitation in industrial processes still suffers from technical limits of samples upscale and reproducibility other than a still moderate comprehension of their action mechanism in the process. This concept article offers a comprehensive and exhaustive "journey" through the most representative lightweight hetero-doped C-based electrocatalysts and their performance in the 2e- ORR process. It provides an interpretation of phenomena at the triple-phase interface of solid catalyst, liquid electrolyte and gaseous oxygen based on the doping-driven generation of ideal electronic microenvironments at the catalyst surface.

7.
Pestic Biochem Physiol ; 202: 105956, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38879338

ABSTRACT

Pepper southern blight, caused by Sclerotium rolfsii, is a devastating soil-borne disease resulting in significant loss to pepper, Capsicum annuum L. production. Here, we isolated an antagonistic bacterial strain XQ-29 with antifungal activity against S. rolfsii from rhizospheric soil of pepper. Combining the morphological and biochemical characteristics with the 16S rDNA sequencing, XQ-29 was identified as Streptomyces griseoaurantiacus. It exhibited an inhibition of 96.83% against S. rolfsii and displayed significant inhibitory effects on Botrytis cinerea, Phytophthora capsica and Rhizoctonia solani. Furthermore, XQ-29 significantly reduced the pepper southern blight by 100% and 70.42% during seedling and growth stages, respectively. The antifungal mechanism involved altering the mycelial morphology, disrupting cell wall and membrane integrity, accompanied by accumulation of reactive oxygen species and lipid peroxidation in S. rolfsii mycelia. Furthermore, XQ-29 promoted growth and stimulated resistance of pepper plants by increasing defense-related enzyme activities and upregulating defense-related genes. Correspondingly, XQ-29 harbors numerous functional biosynthesis gene clusters in its genome, including those for siderophores and melanin production. The metabolic constituents present in the ethyl acetate extracts, which exhibited an EC50 value of 85.48 ± 1.62 µg/mL, were identified using LC-MS. Overall, XQ-29 demonstrates significant potential as a biocontrol agent against southern blight disease.


Subject(s)
Botrytis , Capsicum , Plant Diseases , Rhizoctonia , Streptomyces , Plant Diseases/microbiology , Plant Diseases/prevention & control , Capsicum/microbiology , Streptomyces/genetics , Streptomyces/physiology , Botrytis/drug effects , Botrytis/physiology , Rhizoctonia/physiology , Rhizoctonia/drug effects , Basidiomycota/physiology , Phytophthora/physiology , Phytophthora/drug effects , Biological Control Agents/pharmacology , Antifungal Agents/pharmacology
8.
Dent Clin North Am ; 68(3): 495-515, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38879283

ABSTRACT

The use of mandibular repositioning devices (MRDs) in the management of patients with obstructive sleep apnea (OSA) has gained extensive recognition with relevant clinical evidence of its effectiveness. MRDs are designed to advance and hold the mandible in a protrusive position to widen the upper airway and promote air circulation. This review of the MRD aims to provide an evidence-based update on the optimal design features of an MRD, an analysis of the variety of appliances available, and the current understanding of the action mechanism.


Subject(s)
Mandibular Advancement , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/therapy , Mandibular Advancement/instrumentation , Orthodontic Appliance Design
9.
J Agric Food Chem ; 72(20): 11415-11428, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38727515

ABSTRACT

Rice sheath blight, caused by the fungus Rhizoctonia solani, poses a significant threat to rice cultivation globally. This study aimed to investigate the potential mechanisms of action of camphor derivatives against R. solani. Compound 4o exhibited superior fungicidal activities in vitro (EC50 = 6.16 mg/L), and in vivo curative effects (77.5%) at 500 mg/L were significantly (P < 0.01) higher than the positive control validamycin·bacillus (66.1%). Additionally, compound 4o exhibited low cytotoxicity and acute oral toxicity for adult worker honeybees of Apis mellifera L. Mechanistically, compound 4o disrupted mycelial morphology and microstructure, increased cell membrane permeability, and inhibited both PDH and SDH enzyme activities. Molecular docking and molecular dynamics analyses indicated a tight interaction of compound 4o with PDH and SDH active sites. In summary, compound 4o exhibited substantial antifungal efficacy against R. solani, serving as a promising lead compound for further optimization of antifungal agents.


Subject(s)
Camphor , Fungicides, Industrial , Molecular Docking Simulation , Oryza , Plant Diseases , Rhizoctonia , Rhizoctonia/drug effects , Oryza/microbiology , Plant Diseases/microbiology , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Animals , Camphor/pharmacology , Camphor/chemistry , Bees/microbiology , Fungal Proteins/metabolism , Fungal Proteins/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/chemical synthesis , Structure-Activity Relationship
10.
Foods ; 13(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38790749

ABSTRACT

Fresh-cut vegetables are widely consumed, but there is no food preservative available to selectively inhibit vancomycin-resistant E. faecalis, which is a serious health menace in fresh-cut vegetables. To develop a promising food biopreservative, a bacteriocin, paracin wx7, was synthesized, showing selective inhibition against E. faecalis with MIC values of 4-8 µM. It showed instant bactericidal mode within 1 h at high concentrations with concomitant cell lysis against vancomycin-resistant E. faecalis. Its lethal effect was visualized in a dose-dependent manner by PI/SYTO9 staining observation. The results of an in vivo control experiment carried out on E. faecalis in fresh-cut lettuce showed that 99.97% of vancomycin-resistant E. faecalis were dead after 64 µM paracin wx7 treatment for 7 days without influencing total bacteria. Further, the action mechanism of paracin wx7 was investigated. Confocal microscopy showed that paracin wx7 was located both on the cell envelope and in cytoplasm. For the cell envelope, the studies of membrane permeability using SYTOX Green dyeing and DNA leakage revealed that paracin wx7 damaged the membrane integrity of E. faecalis. Simultaneously, it exhibited membrane depolarization after analysis using DiSC3(5). Damage to the cell envelope resulted in cell deformation observed by scanning electron microscopy. On entering the cytoplasm, the paracin wx7 induced the production of endogenous reactive oxygen species.

11.
Nat Prod Res ; : 1-5, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38721687

ABSTRACT

A new triterpenoid compound 1* (scandine A1) was obtained from 95% ethanol extract of Uncaria laevigata. Meanwhile, eleven described compounds were also isolated for the first time from Uncaria laevigata. Herein, compound 2 exhibited strong diastolic cardio-cerebrovascular activity (EC50BA = 9.22 µM and EC50CA = 14.65 µM), which was not been previously described. Compound 1* also showed certain diastolic cardio-cerebrovasculary activity. Network pharmacology indicated that the diastolic cardio-cerebrovascular activity of compound 2 was most correlated with the Ras signalling pathway. Molecular docking confirmed that it exhibited strong binding activity with target protein (matrix metalloproteinase inhibitor-1). Moreover, compound 2 demonstrated significant potential on cardio-cerebrovascular activity in vitro. Overall, compounds 1* and 2 with good diastolic cardio-cerebrovascular activity were discovered in this work.

12.
J Ethnopharmacol ; 331: 118262, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38670406

ABSTRACT

ETHNOPHARMACOLOGIC RELEVANCE: The leaves of Nelumbo nucifera Gaertn. Are recorded in the earliest written documentation of traditional Chinese medicinal as "Ben Cao Gang Mu", a medicinal herb for blood clotting, dysentery and dizziness. Nuciferine, one of N. nucifera Gaertn. leaf extracts, has been shown to possess several pharmacological properties, including but not limited to ameliorating hyperlipidemia, stimulating insulin secretion, inducing vasodilation, reducing blood pressure, and demonstrating anti-arrhythmic properties. AIM OF THE STUDY: In light of the latest research findings on nuciferine, this article provides a comprehensive overview of its chemical properties, pharmacological activities, and the underlying regulatory mechanisms. It aims to serve as a dependable reference for further investigations into the pharmacological effects and mechanisms of nuciferine. MATERIALS AND METHODS: Use Google Scholar, Scifinder, PubMed, Springer, Elsevier, Wiley, Web of Science and other online database search to collect the literature on extraction, separation, structural analysis and pharmacological activity of nuciferine published before November 2023. The key words are "extraction", "isolation", "purification" and "pharmacological action" and "nuciferine". RESULTS: Nuciferine has been widely used in the treatment of ameliorating hyperlipidemia and lose weight, Nuciferine is a monomeric aporphine alkaloid extracted from the leaves of the plant Nymphaea caerulea and Nelumbo nucifera Gaertn. Nuciferine has pharmacological activities such as relaxing smooth muscles, improving hyperlipidemia, stimulating insulin secretion, vasodilation, inducing hypotension, antiarrhythmic effects, and antimicrobial and anti-HIV activities. These pharmacological properties lay a foundation for the treatment of tumors, inflammation, hyperglycemia, lipid-lowering and weight-loss, oxidative stress and other diseases with nuciferine. CONCLUSION: Nuciferine has been clinically used to treat hyperlipidemia and aid in weight loss due to its effects on lipid levels, insulin secretion, vasodilation, blood pressure reduction, anti-tumor properties, and immune enhancement. However, other potential benefits of nuciferine have not yet been fully explored in clinical practice. Future research should delve deeper into its molecular structure, toxicity, side effects, and clinical pharmacology to uncover its full range of effects and pave the way for its safe and expanded clinical use.


Subject(s)
Aporphines , Nelumbo , Plant Extracts , Nelumbo/chemistry , Humans , Aporphines/pharmacology , Animals , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Leaves
13.
Pest Manag Sci ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676622

ABSTRACT

BACKGROUND: Rice sheath blight caused by Rhizoctonia solani is a severe threat to the yield and quality of rice. Due to the unscientific abuse of common fungicides causing resistance and environmental issues, the development of new fungicides is necessary. In this study, we used citral as the lead compound, designed and synthesized a series of novel citral amide derivatives, and evaluated their antifungal activity and mode of action against R. solani. RESULT: Bioassay results indicated that the antifungal activities of most citral amide derivatives against R. solani were significantly improved compared to citral, with EC50 values ranging from 9.50-27.12 mg L-1. Among them, compound d21 containing the N-(pyridin-4-yl)carboxamide group exhibited in vitro and in vivo fungicidal activities, with curative effects at 500 mg L-1 as effectively as the commercial fungicide validamycin·bacillus. Furthermore, d21 prolonged the lag phase of the growth curve of R. solani, reduced the amount of growth, and inhibited sclerotium germination and formation. Mechanistically, d21 deformed the mycelia, increased cell membrane permeability, and inhibited the activities of antioxidant and tricarboxylic acid cycle (TCA)-related enzymes. Metabolome analysis showed the abundance of some energy-related metabolites within R. solani increased, and simultaneously the antifungal substances secreted by itself reduced. Transcriptome analysis showed that most genes encoding ATP-binding cassette (ABC) transporters and peroxisomes upregulated after the treatment of d21 and cell membrane destruction. CONCLUSION: This study indicates that novel citral amide derivatives possess antifungal activity against R. solani and are expected to develop an alternative option for chemical control of rice sheath blight. © 2024 Society of Chemical Industry.

14.
Chem Biodivers ; 21(6): e202400152, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38600639

ABSTRACT

Thromboembolism is the culprit of cardiovascular diseases, leading to the highest global mortality rate. Anticoagulation emerges as the primary approach for managing thrombotic conditions. Notably, sulfated polysaccharides exhibit favorable anticoagulant efficacy with reduced side effects. This review focuses on the structure-anticoagulant activity relationship of sulfated polysaccharides and the underlying action mechanisms. It is concluded that chlorosulfonicacid-pyridine method serves as the preferred technique to synthesize sulfated polysaccharides. The anticoagulant activity of sulfated polysaccharides is linked to the substitution site of sulfate groups, degree of substitution, molecular weight, main side chain structure, and glycosidic bond conformation. Moreover, sulfated polysaccharides exert anticoagulant activity via various pathways, including the inhibition of blood coagulation factors, activation of antithrombin III and heparin cofactor II, antiplatelet aggregation, and promotion of the fibrinolytic system.


Subject(s)
Anticoagulants , Polysaccharides , Sulfates , Anticoagulants/pharmacology , Anticoagulants/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Structure-Activity Relationship , Humans , Sulfates/chemistry , Sulfates/pharmacology , Animals
15.
Plant Mol Biol ; 114(3): 42, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38630198

ABSTRACT

Continuous cropping of faba bean (Vicia faba L.) has led to a high incidence of wilt disease. The implementation of an intercropping system involving wheat and faba bean can effectively control the propagation of faba bean wilt disease. To investigate the mechanisms of wheat in mitigating faba bean wilt disease in a wheat-faba bean intercropping system. A comprehensive investigation was conducted to assess the temporal variations in Fusarium oxysporum f. sp. fabae (FOF) on the chemotaxis of benzoxazinoids (BXs) and wheat root through indoor culture tests. The effects of BXs on FOF mycelial growth, spore germination, spore production, and electrical conductivity were examined. The influence of BXs on the ultrastructure of FOF was investigated through transmission electron microscopy. Eukaryotic mRNA sequencing was utilized to analyze the differentially expressed genes in FOF upon treatment with BXs. FOF exhibited a significant positive chemotactic effect on BXs in wheat roots and root secretions. BXs possessed the potential to exert significant allelopathic effects on the mycelial growth, spore germination, and sporulation of FOF. In addition, BXs demonstrated a remarkable ability to disrupt the structural integrity and stability of the membrane and cell wall of the FOF mycelia. BXs possessed the capability of posing threats to the integrity and stability of the cell membrane and cell wall. This ultimately resulted in physiological dysfunction, effectively inhibiting the regular growth and developmental processes of the FOF.


Subject(s)
Benzoxazines , Fusarium , Vicia faba , Cell Wall , Triticum , Growth and Development
16.
Biomed Chromatogr ; 38(7): e5870, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38664069

ABSTRACT

Spleen deficiency can lead to various abnormal physiological functions of the spleen. Atractylodis Macrocephalae Rhizoma (AMR) is a traditional Chinese medicine used to invigorate the spleen and tonify qi. The study aimed to identify the primary active components influencing the efficacy of AMR in strengthening the spleen and replenishing qi through spectrum-effect relationship and chemometrics. Network pharmacology was used to investigate the mechanism by which AMR strengthens the spleen and replenishes qi, with molecular docking utilized for validation purposes. The findings indicated that bran-fried AMR exhibited superior efficacy, with atractylenolides and atractylone identified as the primary active constituents. Atractylenolide II emerged as the most influential component impacting the effectiveness of AMR, while the key target was androgen receptor. Furthermore, crucial pathways implicated included the mitogen-activated protein cascade (MAPK) cascade, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, and RNA polymerase II sequence-specific DNA-binding transcription factor binding. In summary, our study has identified the primary active components associated with the efficacy of AMR and has provided an initial exploration of its mechanism of action. This offers a theoretical foundation for future investigations into the material basis and molecular mechanisms underlying the pharmacodynamics of AMR.


Subject(s)
Atractylodes , Drugs, Chinese Herbal , Lactones , Molecular Docking Simulation , Network Pharmacology , Sesquiterpenes , Spleen , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Animals , Atractylodes/chemistry , Lactones/chemistry , Lactones/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Spleen/drug effects , Spleen/metabolism , Rhizome/chemistry , Male
17.
Mol Divers ; 2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38584199

ABSTRACT

In this paper, a series of phenoxypyridine-containing chalcone derivatives (L1-L28) were designed and synthesized, characterized on NMR and HRMS. Ningnanmycin (NNM) was used as a control agent. The results of the antiviral activity testing showed that the curative activity EC50 values of L1 and L4 against TMV were 140.5 and 90.7 µg/mL, respectively, which were superior to that of NNM (148.3 µg/mL). The EC50 values of 154.1, 102.6 and 140.0 µg/mL for the anti-TMV protective activities of L1, L4 and L15 were superior to that of NNM (188.2 µg/mL). The mechanism of action between L4 and NNM and tobacco mosaic virus capsid protein (TMV-CP) was preliminarily investigated. The results of microscale thermophoresis (MST) experiments showed that L4 had a strong binding affinity for TMV-CP with a dissociation constant Kd value of 0.00149 µM, which was better than that of NNM (2.73016 µM). The results of molecular docking experiments showed that L4 formed shorter hydrogen bonds with amino acid residues of TMV-CP than NNM and formed more amino acid residues than NNM, which indicated that L4 was more tightly bound to TMV-CP. This study suggested that phenoxypyridine-containing chalcone derivatives can be used as new anti-TMV drugs through further research and development.

18.
Pest Manag Sci ; 80(8): 3988-3996, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38529554

ABSTRACT

BACKGROUND: To further develop potential natural fungicides, two series of new acrylopimaric acid triazole derivatives were synthesized, and their antifungal activities were tested and evaluated. RESULTS: In vitro antifungal activity results indicated that compound 5m exhibited significant inhibitory activity against Rhizoctonia solani with an half maximal effective concentration (EC50) value of 1.528 mg/L. Its antifungal effect was comparable to that of the commercially available fungicide fluconazole, epoxiconazole and propiconazole (EC50 values of 1.441, 0.815 and 1.173 mg/L). Subsequently, in vivo studies were conducted on compound 5m, which revealed its significant protective and curative effects against R. solani. In addition, physiological and biochemical studies showed that compound 5m could disrupt the morphology and ultrastructure of R. solani mycelium, increase cell membrane permeability, inhibit ergosterol synthesis, and enhance the activity of defense enzymes in rice plants. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies revealed that the molecular structure significantly influenced the binding of compound 5m to the receptor, thereby enhancing its antifungal activity. CONCLUSION: Compound 5m exhibits excellent antifungal activity against R. solani, making it a promising candidate fungicide for the prevention and control of R. solani. © 2024 Society of Chemical Industry.


Subject(s)
Fungicides, Industrial , Rhizoctonia , Triazoles , Triazoles/pharmacology , Triazoles/chemistry , Rhizoctonia/drug effects , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Quantitative Structure-Activity Relationship , Oryza , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Plant Diseases/microbiology , Plant Diseases/prevention & control
19.
Drug Metab Rev ; 56(2): 127-144, 2024.
Article in English | MEDLINE | ID: mdl-38445647

ABSTRACT

Severe acute respiratory syndrome 2 (SARS-CoV-2) caused the emergence of the COVID-19 pandemic all over the world. Several studies have suggested that antiviral drugs such as favipiravir (FAV), remdesivir (RDV), and lopinavir (LPV) may potentially prevent the spread of the virus in the host cells and person-to-person transmission. Simultaneously with the widespread use of these drugs, their stability and action mechanism studies have also attracted the attention of many researchers. This review focuses on the action mechanism, metabolites and degradation products of these antiviral drugs (FAV, RDV and LPV) and demonstrates various methods for their quantification and discrimination in the different biological samples. Herein, the instrumental methods for analysis of the main form of drugs or their metabolite and degradation products are classified into two types: optical and chromatography methods which the last one in combination with various detectors provides a powerful method for routine and stability analyses. Some representative studies are reported in this review and the details of them are carefully explained. It is hoped that this review will be a good guideline study and provide a better understanding of these drugs from the aspects investigated in this study.


Subject(s)
Adenosine Monophosphate , Adenosine Monophosphate/analogs & derivatives , Alanine , Alanine/analogs & derivatives , Amides , Antiviral Agents , COVID-19 Drug Treatment , Lopinavir , Pyrazines , Pyrazines/metabolism , Amides/metabolism , Amides/chemistry , Antiviral Agents/pharmacology , Adenosine Monophosphate/metabolism , Humans , Alanine/metabolism , Lopinavir/therapeutic use , Lopinavir/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Animals
20.
Molecules ; 29(6)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38542897

ABSTRACT

Polymer-modified cement-based materials have been widely used in building materials. Polymers play a crucial role in improving the performance of cement-based materials. At the same time, different polymers are added according to specific special requirements to meet the needs of the industry. Therefore, this paper reviewed the research on the performance and mechanism of acrylic lotion in modifying cement-based materials. Firstly, the role of acrylate lotion in the improvement of the volume stability, mechanical properties, and durability of cement-based materials was discussed to explore the advantages and disadvantages further, optimize the application of polymer in cement-based materials according to the performance improvement, and amplify the advantages of polymer modification. Secondly, the physicochemical mechanism of acrylate-lotion-modified cement-based materials was discussed, and the products and reactants of acrylate lotion in the reaction process of cement-based materials, as well as the interaction mechanism of acrylic lotion and cement hydrates, were clarified. Cement hydration is a crucial step in exploring the mechanism of polymer-modified cement-based materials. Due to the acrylate lotion filled on the cement surface and the physical and chemical interaction between them, the cement hydration is delayed, resulting in the cement retarding phenomenon. This paper describes its mechanism. Finally, the improvement effect of acrylate lotion on the performance of cement-based materials was reviewed, the research methods of mechanism research on acrylate-lotion-modified cement-based materials were evaluated, and suggestions for future research methods were provided.

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