synthesizing new quinoline analogues as newlinepotential antimycobacterial agents

Abstract

Molecular hybridization is a developing approach to design novel medicinal newlinecompounds by merger of two or more biological subunits of known therapeutic agents. In newlinethe present research work, with the aim of synthesizing new quinoline analogues as newlinepotential antimycobacterial agents, we have synthesized various substituted quinoline newlinederivatives like 4-aminoquinoline based anthranilamide Schiff bases, 7-chloro-4- newlinephenoxyquinoline analogues and 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one newlineanalogues. Most of the synthesized compounds were characterized by IR and newline1 newlineH-NMR newlinespectroscopy, and selected compounds were confirmed via LC-MS. Further, all the newlinesynthesized compounds were evaluated for in vitro antimycobacterial activity against newlineMycobacterium tuberculosis H37Rv strain, and selected compounds were evaluated for newlinecytotoxicity activity against normal VERO cell line. newlineResults revealed that majority of the synthesized compounds exhibited minimum newlineinhibitory concentration ranging from 25 and#956;M to 0.78 and#956;M. Among fifty seven synthesized newlinederivatives, fourteen quinoline analogues (4c, 4h, 4i, 4o, 4r, 4u, 15b, 15c, 15f, 18e-18i) newlinedisplayed antitubercular activity at MIC values below 3.12 µM. Compounds 4h and 4i newlinestand out showing MIC values of 0.78 µM and 1.56 µM respectively. Selected newlinecompounds (4h, 4i, 15b, 15c, 15f, 18e, 18g) were further screened for MTB DNA gyrase newlineenzyme inhibition. In addition, molecular docking simulation studies were also carried newlineout in order to better understand the hypothetical binding interactions at Gyr B ATPase newlineactive domain of Mycobacterium smegmatis (PDB ID 4B6C). newlineResults suggested that some of the synthesized compounds have a great potential newlinefor further optimization and development as new antitubercular agents. newline