Design, Synthesis and Biological Evaluation of Quinoline Derivatives as Anti-Tubercular Agents

Abstract

Molecular hybridization is a developing approach to design novel medicinal compounds by merger of two or more biological subunits of known therapeutic agents. The use of current antimycobacterial drugs has been questioned due to their ineffectiveness cause by overuse of them which ultimately leads to antimycobacterial resistance. In the present research work, with the aim of design, synthesize and biological evaluation of quinoline analogues as potential antimycobacterial agents, we have designed various substituted quinoline derivatives by using VLife MDS 4.6 softwere. From that the five compounds R1, R2, R3, R4 and R5 showed the Hydrogen bonding with the significant dock score compared to standard drug Isoniazid (INH). Compound R1 has a dock score of -6.8746, R2 has -6.7128, R3, R4, & R5 has -6.6633, -6.4582, and -6.2401, respectively. These selected compounds were synthesized. All the synthesized compounds were characterized by IR and 1H-NMR spectroscopy, and selected compounds were confirmed via LC-MS. Further, all the synthesized compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv strain by using Microplate Alamar Blue Assay. The investigation of antimycobacterial screening data revealed that all the tested compounds show significant activity. The compounds R1-R5 were screened for antimycobacterial activity against Mtb H37Rv strain. DMSO was used as the negative control, and isoniazid (INH) was used as the positive control. The compound R2 showed the significant activity than the other four compounds.