噻吩衍生物的设计、合成、生物学评价和分子对接研究

IF 2.2 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY Journal of the Iranian Chemical Society Pub Date : 2024-09-07 DOI:10.1007/s13738-024-03088-6
Rashmi Shah, Prabhakar Kumar Verma, Manisha Shah, Satendra Kumar
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引用次数: 0

摘要

研究人员采用 Gewald 合成法合成了一系列 1-(2-氨基-2,4,5,6,7,7a-六氢苯并[b]-3-基)-3-取代苯基丙烷-1,3-二酮衍生物,第一步通过 Baker-Venkataraman 重排反应生成了标题化合物。生成的衍生物的傅立叶变换红外光谱、质谱和 1H NMR 结果均得到验证。研究人员还考察了合成化合物的生物潜力,如抗菌、抗氧化和抗霉菌活性,这些化合物对一种毒性特别强的 MTB 菌株(MTB H37Ra)具有抗菌、抗氧化和抗霉菌活性。抗菌筛选结果表明,化合物 S17 对金黄色葡萄球菌(MIC = 16.87 µM)和枯草杆菌(MIC = 9.45 µM)和革兰氏阴性菌如大肠杆菌(MIC = 16.87 µM)的抗菌剂,化合物 S7 对伤寒沙门氏菌(MIC = 9.74 µM)的抗菌剂,化合物 S16 对白色念珠菌和黑曲霉(MIC = 15.23 µM)均显示出显著的抗真菌活性。标准药物头孢羟氨苄(抗菌)对金黄色葡萄球菌、枯草杆菌、大肠杆菌和伤寒杆菌的 MIC 值分别为 16.40 µM、32.80 µM、16.40 µM 和 16.40 µM,氟康唑(抗真菌)对白色念珠菌和黑曲霉菌株的 MIC 值均为 20.40 µM。根据抗氧化筛选结果,与标准药物抗坏血酸(IC50 值为 44.91 µg/mL)相比,化合物 S10 表现出良好的抗氧化活性,IC50 值为 45.29 µg/mL。体外抗结核筛选结果表明,化合物 S23 有效,其 MIC 值为 78.125 µg/mL。对 "DprE1-脱癸烯酰基磷酰-β-D-核糖-2′-epimerase "酶活性位点的分子对接研究表明,化合物 S23 的结合模式与原生配体相似,且对接得分更高,这有助于理解和开发配体与蛋白质相互作用的模型。化合物 S23 的对接得分为-8.516,而异烟肼的对接得分为-6.315,两者相比,化合物 S23 的对接得分更高,这将为今后抑制 MTB 建立基本的结构框架。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Design, synthesis, biological evaluation and molecular docking studies of thiophene derivatives

A series of 1-(2-amino-2,4,5,6,7,7a-hexahydrobenzo[b]-3-yl)-3-substitued-phenylpropane-1,3-dionederivatives were synthesized using the Gewald synthesis in first step which is followed by Baker−Venkataraman rearrangement to yield title compounds. The FTIR, MS and 1H NMR results of the produced derivatives were validated. The biological potential such as antimicrobial, antioxidant and antimycobacterial activity against a particularly virulent strain of MTB (MTB H37Ra) of the synthesized compounds were examined. Antimicrobial screening outcomes showed that compound S17 turned to be the most effective antibacterial agent against Gram positive bacteria such as Staphylococcus aureus (MIC = 16.87 µM) and Bacillus subtilis (MIC = 9.45 µM) and Gram negative bacteria such as Escherichia coli (MIC = 16.87 µM) and compound S7 against Salmonella typhi (MIC = 9.74 µM) and compound S16 displayed remarkable antifungal activity toward each Candida albicans and Aspergillus niger (MIC = 15.23 µM). The standard drugs, cefadroxil (antibacterial), have MIC value against S. aureus, B. subtilis, E. coli and S. Typhi are 16.40 µM, 32.80 µM, 16.40 µM and 16.40 µM, respectively, and fluconazole (antifungal) has MIC value 20.40 µM against both the C. albicans and A.niger strain. In comparison with ascorbic acid, a standard drug (IC50 44.91 µg/mL), compound S10 demonstrated good antioxidant activity, with an IC50 value of 45.29 µg/mL, according to the results of the antioxidant screening. The results of the in vitro antituberculosis screening showed that compound S23 was found to be effective with an MIC value of 78.125 µg/mL. Molecular docking study of an enzymatic active site of “DprE1-decaprenylphosphoryl-β-D-ribose-2′-epimerase” shows a comparable binding mode to the native ligand with better docking score which contributes in understanding and development of models for ligand–protein interactions. Compound S23 showed better docking score of − 8.516 as compared to the Isoniazid with the docking score of − 6.315 which in future will create the fundamental structural framework for MTB inhibition.

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CiteScore
4.40
自引率
8.30%
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230
审稿时长
5.6 months
期刊介绍: JICS is an international journal covering general fields of chemistry. JICS welcomes high quality original papers in English dealing with experimental, theoretical and applied research related to all branches of chemistry. These include the fields of analytical, inorganic, organic and physical chemistry as well as the chemical biology area. Review articles discussing specific areas of chemistry of current chemical or biological importance are also published. JICS ensures visibility of your research results to a worldwide audience in science. You are kindly invited to submit your manuscript to the Editor-in-Chief or Regional Editor. All contributions in the form of original papers or short communications will be peer reviewed and published free of charge after acceptance.
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