Hybrid Quinazoline 1,3,5-Triazines as Epidermal Growth Factor Receptor (EGFR) Inhibitors with Anticancer Activity: Design, Synthesis, and Computational Study

We report a series of hybrid quinazoline-1,3,5-triazine derivatives as EGFR inhibitors, which were synthesised and tested by using a variety of in vitro, in silico, and in vivo techniques. The derivatives were found to be active against different cancer cell lines and nontoxic against normal ones, with compounds 7 c, 7 d, 7 e, and 7 j being the most potent ones. The derivatives were also evaluated for angiogenesis inhibition potency in chicken eggs, and molecular docking and dynamics simulation studies were carried out to elucidate the fundamental substituent groups essential for their bioactivity. Additionally, a SAR study of the derivatives was performed for future compound optimisation. These studies suggested that the derivatives have a high affinity towards EGFR with favourable pharmacological properties. The most active compound (7 e) was further evaluated for in vivo anticancer activity against DMBA-induced tumours in female Sprague-Dawley rats as well as its effects on plasma antioxidant status, biotransformation enzymes, and lipid profile. The study suggested that 7 e has lead properties against breast cancer and can serve as a starting compound for further development of anti-EGFR compounds.

Automated summary

A series of hybrid quinazoline-1,3,5-triazine derivatives as EGFR inhibitors were synthesised and tested, showing activity against cancer cell lines with compounds 7c, 7d, 7e, and 7j being the most potent. In vitro and in silico techniques were used to elucidate essential substituent groups, with SAR studies performed for compound optimisation. Compound 7e showed promising activity against breast cancer in vivo and may serve as a lead compound for further anti-EGFR drug development.