Click approach for synthesis of 3,4-dihydro-2(1H) quinolinone, coumarin moored 1,2,3-triazoles as inhibitor of mycobacteria tuberculosis H37RV, their antioxidant, cytotoxicity and in-silico studies

Abstract

In search of new potent molecules against tuberculosis, 3,4-dihydro-2(1H)-quinolinone based 1,2,3-triazoles were synthesized efficiently by means of click chemistry and their structures were confirmed by spectral data. Among the synthesized twelve novel molecules, seven are hybrid of 3,4-dihydro-2(1H)-quinolinone, 1,2,3–1H-triazole nucleus with different coumarin derivatives and in remaining molecules coumarin is replaced by alkyl, aryl, and pyranose derivatives. Among the synthesized compounds, eight were screened for anti-TB activity against H37Rv strain and found to have good inhibition activity with lower MIC values (2.7–10.6 µM). Compound 6 h with (6-(acetoxymethyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate) substitution is most active against MTB. Further their antioxidant activity was assessed using DPPH assay and the compounds have shown moderate to low activity compared to standard ascorbic acid. The cytotoxicity of the synthesised compounds against lung cancer cell lines exhibited good to moderate activity and do not induce significant toxicity. In Superoxide dismutase(SOD) enzyme activity studies some of the compounds exhibited promising activity. The interactions of the molecules were studied against DprE1 protein of MTB through molecular docking.