Novel quinazolin-4(3H)-ones 4–27 were synthesized. Compounds 4, 11, and 20 showed potential anti-tumour activities. 4, 11, and 20 blocked EGFR/VEGFR-2 and triggered apoptosis. Compound 4 showed the most potent activity against EGFR/VEGFR-2.

Cancer remains a leading cause of death worldwide, often resulting from uncontrolled growth in various organs. Protein kinase inhibitors represent an important class of targeted cancer therapies. Recently, the kinases BRAF and VEGFR-2 have shown synergistic effects on tumor progression. Seeking to develop dual BRAF/VEGFR-2 inhibitors, we synthesized 18 amino-benzothiazole derivatives with structural similarities to reported dual inhibitors. Four compounds—4a, 4f, 4l, and 4r—demonstrated remarkable cytotoxicity, with IC₅₀ values ranging from 3.58 to 15.36 μM, against three cancer cell lines. Furthermore, these compounds showed IC₅₀ values of 38.77–66.22 μM in the case of a normal cell line, which was significantly safer than the reference, sorafenib. Subsequent investigation revealed that compound 4f exhibited the capacity to inhibit the BRAF and VEGFR-2 enzymes, with IC₅₀ values similar to sorafenib (0.071 and 0.194 μM, respectively). Moreover, compound 4f caused G2-M- and S-phase cycle arrest. Molecular modeling demonstrated binding patterns compatible with inhibition for both targets, where 4f exerted the critical interactions in the BRAF site and interacted in the VEGFR-2 site in a manner akin to sorafenib, demonstrating affinity similar to dabrafenib.

In response to the urgent need for new anti-proliferative agents, four novel series of triazolopyrimidine compounds (7a–e, 9a–d, 11a–f, and 13a–e) were synthesized and evaluated for in vitro and in vivo anticancer efficacy.