Synthesis and Docking of Triazole, Pyrazole, and Schiff Base Linked Quinazolinones for Anticancer and Antimicrobial Applications

Quinazolinone derivatives bearing a trifluoromethyl substituent have attracted considerable attention. A series of novel Schiffs base, pyrazole and triazolefunctionalized quinazolinone derivatives were prepared starting from 2-amino-6-(trifluoromethyl)benzonitrile 1 on hydrolysis obtained 2- amino-6-(trifluoromethyl)benzoic acid 2, further reacts with phenylisocyanate gives 2-mercapto-3- phenyl-5-(trifluoromethyl)quinazolin-4(3H)-one 3, which upon reaction with POCl3converts to 2- chloro-3-phenyl-5-(trifluoromethyl)quinazolin-4(3H)-one 4. Further chloro derivative on reaction with hydrazinehydrate forms 2-hydrazinyl-3-phenyl-5-(trifluoromethyl)quinazolin-4(3H)-one 5. Compound 5, on further reaction with aromatic acids, 3-oxo-3-phenylpropanenitrile, and aromatic aldehydes, to get triazole, pyrazole, and Schiff's base functionalized quinazolinone derivatives 6a-d, 7a-d and 8a-d. All the final compounds evaluated for anticancer activity against four human cancer cell lines such as ‘HeLa-Cervical cancer (CCL-2); COLO 205-Colon cancer (CCL-222); HepG2-Liver cancer (HB-8065); MCF7-Breast cancer (HTB-22) and normal cell line such as HEK-293 – Human Embryonic Kidney cells (CRL-1573)’ and promising compounds which showed good activity have been identified and docking interactions are also identified. All the synthesized compounds were screened against Gram-positive and Gram-negative bacterial strains and one Candida strain by the well diffusion method. Some of the compounds showed promising antibacterial activity against bacterial strains as compared to the standards.