富氟嘧啶-5-碳腈抗H37Rv受体结核药物的合成

IF 1.3 3区化学 Q3 CHEMISTRY, ORGANIC

Heterocyclic Communications Pub Date : 2022-01-01 DOI:10.1515/hc-2022-0010

K. Kapadiya, K. Kavadia, V. Khedkar, P. Dholaria, A. Jivani, R. Khunt

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引用次数: 1

摘要

摘要本研究的目的是用三步法制备4-氨基-2-（3-氟-5-（三氟甲基）苯基）-6-芳基嘧啶-5-腈（6a–6h）的各种衍生物。在体外筛选该衍生物对结核分枝杆菌菌株H37Rv的活性。活性以最小抑制浓度（MIC）表示，单位为μg/mL（μM）。8个化合物对结核分枝杆菌H37Rv具有活性，其中6f的MIC、IC50（53 μM）和IC90（62 μM）。化合物6f的最低杀菌浓度高于其MIC，且与浓度的依赖性更强。化合物6f在低氧条件下对结核分枝杆菌H37Rv的活性高于甲硝唑，并且在不同的治疗和非结核分枝杆菌中没有显示出良好的效力。此外，针对分枝杆菌烯醇ACP还原酶（InhA）的分子对接研究可以为可能的作用机制提供有价值的见解，这可以为铅的优化设定主题。图形摘要

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Synthesis of fluoro-rich pyrimidine-5-carbonitriles as antitubercular agents against H37Rv receptor

Abstract The purpose of this study was to prepare various derivatives of 4-amino-2-(3-fluoro-5-(trifluoromethyl)phenyl)-6-arylpyrimidine-5-carbonitrile (6a–6h) using a three-step procedure. The derivatives were screened in vitro for activity against Mycobacterium tuberculosis strain H37Rv. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL (μM). Eight compounds showed activity against Mtb H37Rv, and among them, 6f showed the best value of MIC, IC50 (53 μM) and IC90 (62 μM). Minimum bactericidal concentration of compound 6f was higher than its MIC and was more time-dependent than the concentration. Compound 6f was more active against M. tuberculosis H37Rv under low oxygen than metronidazole and did not show good potency in different treatments and non-tuberculous mycobacteria. Furthermore, a molecular docking study against mycobacterial enoyl-ACP reductase (InhA) could provide valuable insights into the plausible mechanism of action, which could set the theme for lead optimization. Graphical abstract

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来源期刊

Heterocyclic Communications 化学-有机化学

CiteScore

3.80

自引率

4.30%

发文量

审稿时长

1.4 months

期刊介绍： Heterocyclic Communications (HC) is a bimonthly, peer-reviewed journal publishing preliminary communications, research articles, and reviews on significant developments in all phases of heterocyclic chemistry, including general synthesis, natural products, computational analysis, considerable biological activity and inorganic ring systems. Clear presentation of experimental and computational data is strongly emphasized. Heterocyclic chemistry is a rapidly growing field. By some estimates original research papers in heterocyclic chemistry have increased to more than 60% of the current organic chemistry literature published. This explosive growth is even greater when considering heterocyclic research published in materials science, physical, biophysical, analytical, bioorganic, pharmaceutical, medicinal and natural products journals. There is a need, therefore, for a journal dedicated explicitly to heterocyclic chemistry and the properties of heterocyclic compounds.