Design, synthesis, anti-tubercular activity, and computational studies of novel 3-(quinolin-3-yl)-1-phenylprop-2-en-1-one derivatives

Tuberculosis (TB) is a contagious disease caused by M. tuberculosis (Mtb) affecting people across the globe. Quinoline and chalcone cores have good anti-tubercular properties; thus, we have designed a hybrid scaffold containing quinoline and chalcone. A series of 3-(quinolin-3-yl)-1-phenylprop-2-en-1-one analogs 7a-p and 8a-k were synthesized through different reactions involving nucleophilic substitution, Vilsmeier Haack formylation, Claisen Schmidt condensation, and demethylation. Spectroscopic methods, including H-1 NMR, C-13 NMR, IR, and HRMS, were used to characterize all synthesized compounds. The anti-tubercular activity of compounds 7a-p and 8a-k was assessed against Mtb H(37)Rv (ATCC 27294). These compounds demonstrated anti-tubercular activity against H37Rv in the range of 6.25-50 mu M. Swiss ADME's in silico computational studies showed that the ADME parameters were better and had a good pharmacokinetic profile. The compounds 8a, 7a, and 7p showed the most potential as anti-TB activity against Mtb H37Rv in this study, with MIC values of 6.25 mu M, 12.5 mu M, and 10 mu M, respectively. [Graphics]