Synthesis, antituberculosis studies and biological evaluation of new quinoline derivatives carrying 1,2,4-oxadiazole moiety

A new series of quinoline carrying 1,2,4-oxadiazole moiety have been synthesized and evaluated for their antituberculosis studies. Majority of them showed moderate to good antituberculosis activity. [Display omitted] •Compound QD-18, QD-19, QD-20 and QD-21 are potent against Mtb WT H37Rv with encouraging MIC values.•Four identified compounds are tuberculosis specific, orally bioavailable, non-cytotoxic and metabolically stable.•Compound QD-20 and QD-21 exhibited an excellent pharmacokinetic profile.•A series of quinoline hybrids synthesized are a new class of anti-tubercular molecules. Tuberculosis is the infectious disease caused by mycobacterium tuberculosis (Mtb), responsible for the utmost number of deaths annually across the world. Herein, twenty-one new substituted 1,2,4-oxadiazol-3-ylmethyl-piperazin-1-yl-quinoline derivatives were designed and synthesized through multistep synthesis followed by in vitro evaluation of their antitubercular potential against Mtb WT H37Rv. The compound QD-18 was found to be promising with MIC value of 0.5 µg/ml and QD-19 to QD-21 were also remarkable with MIC value of 0.25 µg/ml. Additionally, we have carried out experiments to confirm the metabolic stability, cytotoxicity and pharmacokinetics of these compounds along with kill kinetics of QD-18. These compounds were found to be orally bioavailable and highly effective. Altogether, these results indicate that QD-18, QD-19, QD-20 and QD-21 are promising lead compounds for the development of a novel chemical class of antitubercular drugs.