Novel triazoloquinazoline derivatives as VEGFR inhibitors: synthesis, cytotoxic evaluation and in silico studies

New triazoloquinazoline derivatives were synthesized to explore their cytotoxic activity on various cancer cell lines, prompted by the need for effective anticancer agents. All synthesized compounds were confirmed by spectroscopic methods and tested in vitro for their inhibitory activities against hepatocellular carcinoma (HepG-2), breast cancer (MCF-7), and prostate cancer (PC3) cell lines. Ten compounds were tested in vitro to explore their inhibitory activity against the VEGFR-2. Additionally, various studies were investigated for the most active compound 6, including cell cycle analysis, apoptotic activity assessment, effect on gene expression, safety profiling, molecular docking, MD simulation, and ADMET analysis. Compounds 3a, 3c, and 6 exhibited higher cytotoxic activity against MCF-7 than doxorubicin. Compound 6 was most potent, arresting the cell cycle at G1 phase and showing proapoptotic action. It significantly inhibited VEGFR-2 and altered gene expression, promoting BAX, P21, and P53 while downregulating BCL-2. Docking and MD simulations indicated stable interaction with VEGFR-2, safety, and ADMET profiles suggested favorable drug-likeness and safety. Compound 6 has shown promising anticancer potential, particularly against breast cancer, but further research is needed to confirm these findings and address long-term safety.