19 Schiff bases as antimycobacterial agents: synthesis, molecular docking and a plausible mechanism of action

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.