19 Schiff Bases as Antimycobacterial Agents: Synthesis, Molecular Docking and a Plausible Mechanism of Action

作者：Yuxiang Cai, Junxian Chen, Hongmei Dong, Zai‐Chang Yang · 发表于：Future Medicinal Chemistry · 年份：2024 · DOI：10.4155/fmc-2023-0305 · 被引用次数：4 · 研究领域：Tuberculosis Research and Epidemiology、Biochemical and Molecular Research、Cancer therapeutics and mechanisms

Aim: To discover novel anti-Mycobacterium tuberculosis (Mtb) drugs, 19 compounds were synthesized; their anti-Mtb effects were evaluated and mechanisms of action were preliminarily explored. Materials & methods: The compounds were synthesized and their anti-Mtb activity was elucidated using resazurin microtiter assays. The plausible target of the potential compound was investigated by microimaging techniques, gas chromatography–mass spectrometry analysis and molecular docking. Results: 19 compounds inhibited Mtb growth with minimum inhibitory concentrations ranging from 1 to 32 μg/ml. Compounds 1–17 showed inhibition of Mtb KatG enzyme. Compound 19, the most potent, might be an inhibitor of Pks13 polyketide synthase. Conclusion: This study suggests that 2-((6-fluoropyridin-3-yl)methylene) hydrazine-1-carbothioamide (19) is a potential anti-Mtb lead compound with a novel mechanism of action.