Synthesis, Molecular Docking, and In vitro Antimycobacterial Studies on N'-arylidene-4-nitrobenzohydrazides

Abstract

Background: Mycobacterium tuberculosis (Mtb) is the organism that causes tuberculosis to develop (TB). In 2019, 10 million individuals worldwide contracted tuberculosis, with 1.4 million people dying from the disease each year (World Health Organization, 2021). Hydrazones-hydrazide-based drugs have been shown to be bactericidal against M. tuberculosis replication. Objectives: We herein intended to synthesize a series of acid hydrazones (3a-3l) by condensing 4-nitrobenzohydrazine with substituted aromatic acids in ethanol at room temperature. Materials and Methods: All newly synthesized compounds were characterized by standard spectroscopic techniques. Synthesized compounds were then tested for anti-mycobacterial analysis, H37Rv strains. Molecular docking analysis was performed for three crystal structures of 1ENY, 1TED and 2FUM Mycobacterium tuberculosis receptors. Results: Among all tested molecules, 3i (MIC: 50 μg/mL) and 3b (MIC: 50 μg/mL) were found to best ligands for further development of new anti-TB drug. We noticed that our proposed molecules were having higher docking scores that corresponding standard anti-TB agents such as Ciprofloxacin and Isoniazid. Synthesized compounds were found to have Drug-Likeness properties when tested with Lipinski’s filter for drug-likeness. Conclusion: From our current study, we wish to propose N'-arylidene-4-nitrobenzohydrazides as anti-TB agents. Agents with such system can be developed in future for developments into active lead molecules.