Synthesis of Novel Pyrido[2′,3′:3,4]Pyrazolo[1,5-α]Quinazoline Derivatives, Their Biological Evaluation and Molecular Modelling Studies

A series of novel ethyl 9-(trifluoromethyl) pyrido [2 ',3 ':3,4]pyrazolo[1,5-a]quinazoline-8-carboxylate 4, 9-(trifluoromethyl)pyrido[2 ',3 ':3,4]pyrazolo[1,5-alpha]quinazoline-8-carboxylic acid 5, aryl amide functionalized pyrido[2 ',3 ':3,4]pyrazolo [1,5-alpha] quinazoline derivatives 6a-f, secondary amide functionalized pyrido[2 ',3 ':3,4] pyrazolo[1,5-alpha]quinazoline derivatives 7a-d and primary amide functionalized pyrido[2 ',3 ':3,4]pyrazolo[1,5-alpha] quinazoline derivatives 8a-h were prepared starting from 2(1H)pyridone 1. All the compounds were evaluated for antibacterial activity against Gram-positive and Gram-negative bacterial strains and the compounds 5, 6a, 6c, 6f, 7a, 8c, 8f and 8h exhibited promising antibacterial activity against various bacterial strains. Compound 5 showed high antibacterial (MIC value of 3.9 mu g/mL) and broad-spectrum anti bio-film activity. Compound 5 and 8b also showed good antifungal activity against the tested panel of various Candida strains. Molecular docking studies revealed that, the compound 5 and 8b showed good binding interactions and corroborates with the antifungal results. All the compounds also screened for cytotoxicity and the compounds 7d, 8a, 8b and 8d exhibited above 90% inhibition against MCF7 (breast) cancer cell line and the compounds 6d, 7a, 8a, 8b, 8f and 8g exhibited above 90% inhibition against SKOV3 (ovarian) cell line, with reference to Doxorubicin (Control) drug in terms of inhibition.