Journal of Saudi Chemical Society
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2024
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IF 5.8
Yong Zhang,Mei Zhu,Kun Hu,Xing Liu,Yue Zou,Jixiang Chen
Fluopyram is a highly effective agricultural fungicide targeting succinate dehydrogenase (SDH). Twenty-six novel amide derivatives containing azetidine were designed and synthesized with fluopyram as the lead, and their biological activities were tested. The results showed that some compounds had obvious antifungal activities against Phomopsis sp., among them, the EC 50 value of compound C24 was 5.7 mg/L, which was significantly better than fluopyram (105.4 mg/L). The curative and protective activities of compound C24 on kiwi fruit infected with Phomopsis sp. were 42.2 and 52.9 %, which were better than that of fluopyram (30.4 and 35.6 %) at 200 mg/L. Moreover, compound C24 exhibited excellent inhibitory against SDH. The results of scanning electron microscopy (SEM) indicated that the mycelium of Phomopsis sp. collapsed or even ruptured after compound C24 treatment. Meanwhile, molecular docking showed that compound C24 was deeply embedded into the SDH binding pocket, and the binding model was stabilized by a cation–π interaction with Cys-40, Tyr-58 and an H-bond with Lys-455 and Asn-452. Compound C24 can provide a valuable idea to find new succinate dehydrogenase inhibitors.
研究领域:
农业化学
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药理学
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真菌学
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DOI
高影响因子
Journal of Pharmaceutical Analysis
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2023
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IF 8.8
Yang Yi,Wenzhe Li,Kefang Liu,Heng Xue,Rong Yu,Meng Zhang,Yang-Oujie Bao,Xinyuan Lai,Jingjing Fan,Yuxi Huang,Jing Wang,Xiaomeng Shi,Junhua Li,Hongping Wei,Kuanhui Xiang,Linjie Li,Rong Zhang,Xin Zhao,Xue Qiao,Hang Yang,Min Ye
Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC 50 of 1.016 μM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
研究领域:
病毒学
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药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2022
·Vol. 10
·期 6
·1841-1853
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IF 3.553
Jun Yang,Shulin Hu,Anqi Liao,Yetian Weng,Shuli Liang,Ying Lin
Current chemical analysis approaches for contaminants have failed to reveal their biotoxicity. Moreover, conventional bioassays are time consuming and exhibit poor repeatability. In this study, we performed the acute toxicity detection of various contaminants (chromium (Cr), cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg), tin (Sn), nickel (Ni), and bisphenol A (BPA)) with four bioluminescent bacteria ( Vibrio qinghaiensis Q67, V. fischeri , Photobacterium phosphoreum T3, and P. phosphoreum 502) using a rapid, flexible, and low-cost bioassay. We found that the temperature affected the bacterial luminescence, and freeze-dried cells exhibited sensitive toxic responses to contaminants. Indeed, the optimized protectants containing 12% (w/v) trehalose, 4% sucrose, and 2% sorbitol displayed better luminescence and toxic sensitivity. Furthermore, freeze-dried powders of these strains were prepared and subjected to acute toxicity detection. The results showed that all contaminants exhibited acute toxicity toward Q67, but the other strains did not show obvious response to nickel and tin. The relative half-maximal effective concentration (EC 50 ) values of BPA, Cr, Cd, Pb, As, Hg, Ni, and Sn to Q67 were 0.674, 1.313, 11.137, 5.921, 4.674, 0.911, 5.941, and 54.077 mg/L, respectively. In addition, the EC 50 values of contaminants toward different strains were suggested to be statistically significant. Freeze-dried Q67 exhibited toxic responses to more contaminants than the other bioluminescent strains; therefore, Q67 was selected to be more suitable than the other strains for single and mixture toxicity detection tests. Compared with other strains, Q67 was more appropriate for the rapid screening of the mixture toxicity of contaminants in samples as a nonspecific screening sensor before the use of standard analysis approaches.
研究领域:
环境科学
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毒理学
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生物技术
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化学分析
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产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2020
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IF 2.751
Xiang Zhou,Yiqiang Ye,Shasha Liu,Wubin Shao,Liwei Liu,Song Yang,Zhibing Wu
Plant viral diseases, known as “plant cancer”, with high contagiosity can substantially reduce crop quality and yield. To identify potential anti- tobacco mosaic virus (TMV) agents with different mechanisms, a series of novel α-aminophosphonate derivatives containing a chalcone moiety were designed and synthesized. Bioassay results revealed that some target compounds exhibited improved curative activity against TMV in vivo, and the EC 50 value of compound B 3 was 356.7 mg L −1 . The activities of the defensive enzymes POD and CAT from tobacco leaves treated with B 3 and B 17 showed that these target compounds could improve the photosynthetic ability of the leaves and activate plant host resistance against TMV infection. The binding constant between B 3 and TMV Coat Protein (CP) (2.51 × 10 8 M −1 ), calculated by the fluorescence titration experiment and docking results, revealed that B 3 has a strong interaction with TMV CP. Further docking analysis revealed that B 3 was embedded between two layers of the TMV CP, which was consistent with the 2:1 binding mode of TMV CP and B 3 determined by the binding affinity experiment. The TEM morphological study of TMV treated with B 3 and B 17 indicated that this series of target compounds may trigger the disassembly of TMV by interacting directly with TMV CP. This study provides new insight for the discovery of antiviral compounds with two different mechanisms of action.
研究领域:
植物病毒学
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有机化学
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植物病理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
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2023
·Vol. 79
·期 5
·1922-1930
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IF 4.1
Zhi Ma,Shuo Qiu,Dong Zhang,Xinying Guo,Yuele Lu,Yongxian Fan,Xiaolong Chen
BACKGROUND Succinate dehydrogenase inhibitor (SDHI) fungicides are an important class of agricultural fungicides with the advantages of high efficiency and a broad bactericidal spectrum. To pursue novel SDHIs, a series of N -substituted dithiin tetracarboximide derivatives were designed, synthesized, and characterized by 1 H NMR, 13 C NMR, and high resolution mass spectrum (HRMS). RESULTS These engineered compounds displayed potent fungicidal activity against phytopathogens, including Sclerotinia sclerotiorum , Botrytis cinerea , and Rhizoctonia solani , comparable with that of the commercial SDHI fungicide boscalid . In particular, compound 18 stood out with prominent activity against S. sclerotiorum with a half-maximal effective concentration (EC 50 ) value of 1.37 μg ml −1 . Compound 1 exhibited the most potent antifungal activity against B. cinerea with EC 50 values of 5.02 μg ml −1 . As for R. solani , 12 and 13 exhibited remarkably inhibitory activity with EC 50 values of 4.26 and 5.76 μg ml −1 , respectively. In the succinate dehydrogenase (SDH) inhibition assay, 13 presented significant inhibitory activity with a half-maximal inhibitory concentration (IC 50 ) value of 15.3 μ m , which was approximately equivalent to that of boscalid (14.2 μ m ). Furthermore, molecular docking studies revealed that 13 could anchor in the binding site of SDH. CONCLUSION Taken together, results suggested that the dithiin tetracarboximide scaffold possessed a huge potential to be developed as novel fungicides and SDHIs. © 2023 Society of Chemical Industry.
研究领域:
农业化学
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药物化学
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植物病理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Zian Mao,Liu Yang,Yishan Lv,Yuchi Chen,Mingyuan Zhou,Chengnan Fang,Bingqi Zhu,Fangmei Zhou,Zhishan Ding
A novel acidic glucuronogalactomannan (STHP-5) was isolated from the aboveground part of Tetrastigma hemsleyanum Diels et Gilg with a molecular weight of 3.225 × 10 5 kDa. Analysis of chain conformation showed STHP-5 was approximately a random coil chain. STHP-5 was composed mainly of galactose, mannose, and glucuronic acid. Linkages of glycosides were measured via methylation analysis and verified by NMR. Based on the structural characterization, the repeat unit of STHP-5 was proposed. In vitro, STHP-5 induced the production of nitric oxide (NO) and secretion of IL-6, MCP-1, and TNF-α in RAW264.7 cells, indicating STHP-5 had stimulatory activity on macrophages. STHP-5 was proven to function as a TLR4 agonist by inducing the secretion of secreted embryonic alkaline phosphatase (SEAP) in HEK-Blue™-hTLR4 cells. The TLR4 activation capacity was quantitatively measured via EC50, and it showed purified polysaccharides had stronger effects (lower EC50) on activating TLR4 compared with crude polysaccharides. In conclusion, our findings suggest STHP-5 may be a novel immunomodulator.
研究领域:
药理学
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免疫学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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