Design, Synthesis, and Anti-Proliferative Action of Purine/Pteridine-Based Derivatives as Dual Inhibitors of EGFR and BRAF.

The investigation of novel EGFR and BRAF dual inhibitors is intended to serve as targeted cancer treatment. Two sets of purine/pteridine-based derivatives were designed and synthesized as EGFR/BRAF dual inhibitors. The majority of the compounds exhibited promising antiproliferative activity on the cancer cell lines tested. Compounds , , and of purine-based and pteridine-based scaffolds were identified as the most potent hits in anti-proliferative screening, with GI values of 38 nM, 46 nM, and 44 nM, respectively. Compounds , , and demonstrated promising EGFR inhibitory activity, with IC values of 87 nM, 98 nM, and 92 nM, respectively, when compared to erlotinib's IC value of 80 nM. According to the results of the BRAF inhibitory assay, BRAF may not be a viable target for this class of organic compounds. Finally, molecular docking studies were carried out at the EGFR and BRAF active sites to suggest possible binding modes.