Synthesis of Novel Pyrido[2′,  3′:3, 4]Pyrazolo[1,  5‐a]Quinazoline Derivatives, Their Biological Evaluation and Molecular Modelling Studies. Issue 27 (18th July 2018)

• Record Type: Journal Article
• Authors: Kumar, Nagiri Ravi; Swaroop, Desireddy Krishna; Punna, Nagender; Sirisha, Kanugala; Ganapathi, Thipparapu; Kumar, Chityal Ganesh; Narsaiah, Banda
• Is Part Of: ChemistrySelect. Volume 3:Issue 27(2018)
• Page Start: 7813
• Page End: 7821
• Publication Date: 2018-07-18
• Subjects: antibacterial -- anti-biofilm -- antifungal -- cytotoxicity -- molecular modelling; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201801186
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: A series of novel ethyl 9‐(trifluoromethyl) pyrido [2′, 3′:3, 4]pyrazolo[1, 5‐ a ]quinazoline‐8‐carboxylate4, 9‐(trifluoromethyl)pyrido[2′, 3′:3, 4]pyrazolo[1, 5‐ a ]quinazoline‐8‐carboxylic acid5, aryl amide functionalized pyrido[2′, 3′:3, 4]pyrazolo [1, 5‐ a ] quinazoline derivatives6 a‐f, secondary amide functionalized pyrido[2′, 3′:3, 4] pyrazolo[1, 5‐ a ]quinazoline derivatives7 a‐d and primary amide functionalized pyrido[2′, 3′:3, 4]pyrazolo[1, 5‐ a ] quinazoline derivatives8 a‐h were prepared starting from 2(1 H )pyridone1 . All the compounds were evaluated for antibacterial activity against Gram‐positive and Gram‐negative bacterial strains and the compounds5, 6 a, 6 c, 6 f, 7 a, 8 c, 8 f and8 h exhibited promising antibacterial activity against various bacterial strains. Compound5 showed high antibacterial (MIC value of 3.9 μg/mL) and broad‐spectrum anti bio‐film activity. Compound5 and8 b also showed good antifungal activity against the tested panel of various Candida strains. Molecular docking studies revealed that, the compound5 and8 b showed good binding interactions and corroborates with the antifungal results. All the compounds also screened for cytotoxicity and the compounds7 d, 8 a, 8 b and8 d exhibited above 90% inhibition against MCF7 (breast) cancer cell line and the compounds6 d, 7 a, 8 a, 8 b, 8 f and8 g exhibited above 90% inhibition against SKOV3 (ovarian) cell line, with reference to Doxorubicin (Control) drug in terms of inhibition. Abstract : Novel pyrido[2′, 3′:3, 4]pyrazolo[1, 5‐a]quinazoline derivatives were prepared and evaluated for antimicrobial and cytotoxic activities. Among all the compounds, 9‐(trifluoromethyl)pyrido[2′, 3′:3, 4]pyrazolo[1, 5‐a]quinazoline‐8‐carboxylic acid (5) and N‐(Furan‐2‐ylmethyl)‐9‐(trifluoromethyl)pyrido[2′, 3′:3, 4]pyrazolo[1, 5‐a]quinazoline‐8‐carboxamide (8 b) exhibited excellent antimicrobial activities. Moreover compound8 b also showed promising cytotoxicity against MCF7 (breast) and SKOV3 (ovarian) cancer cell lines.