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

• Published in: Journal of molecular structure 2022-12, Vol.1269, p.133795, Article 133795
• Main Authors: Hebbar, Nagashree U., Patil, Anilkumar R., Gudimani, Parashuram, Shastri, Samundeeswari L., Shastri, Lokesh A., Joshi, Shrinivas D., Vootla, Shyam Kumar, Khanapure, Sheela, Shettar, Arun K., Sungar, Vinay A.
• Format: Article
• Language: English
• Subjects: 1,2,3-Triazole; 3,4-Dihydro-2(1H)-quinolinone; Click chemistry; Coumarin; Mycobacterium tuberculosis H37Rv
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.133795

•Simple synthetic procedures were employed to synthesize new triazole bridged bi-heterocycles.•Synthesized scaffolds were assessed for their in vitro antitubercular, antioxidant, cytotoxic and superoxide dismutase enzyme activities.•The scaffolds were proven to be potential anti-TB agents.•Molecular docking studies with DprE1 enzyme shown similar interaction of compounds as that of FDO ligand.•The scaffolds may be considered for in vivo use as lead drug. 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. [Display omitted]