Quinazolinone-linked triazole conjugates: Synthesis, biological evaluation, and in silico studies

The present study deals with design and synthesis of quinazolinone-linked triazole conjugates as promising anticancer agents. We have reported the synthesis of twelve new compounds (6a-l) using click chemistry approach. The structures of newly synthesized compounds were confirmed by means of spectroscopic techniques, which included FTIR, 1H NMR, 13C NMR and HRMS. Subsequently, the compounds were screened for their anticancer activities against MCF-7 human breast cancer cell line by using MTT assay. The results demonstrated that seven compounds exhibited excellent anticancer activity with IC50 values ranging from 5.64 to 9.09 μg/mL. Most of the compounds exhibited better cell viability (%) than the control compound, Doxorubicin. Additionally, these newly synthesized compounds were tested for their antimicrobial and antioxidant activities. The results revealed that these compounds show good activities compared with the standard. Drug-likeness and ADMET study displayed desirable properties, and DFT studies confirmed promising electronic characteristics. The in silico studies revealed that the target compounds exhibited strong binding affinity with the selected CDK2 protein structure, with binding affinities ranging from -10.4 to -11.2 kcal/mol. It can be inferred that these conjugates have the potential to be useful frameworks for developing new drugs with a broad spectrum of anticancer activity in the coming years.