New quinoline-based derivatives 3a-d and 4a-d have been designed and synthesized as promising antiproliferative candidates. The designed compounds were tested for their antiproliferative activity against a panel of four human cancer cell lines with GI50 values ranging from 1.40 μM to 5.00 μM relative to doxorubicin (GI50 = 1.20 μM). Compound 4a was the most potent derivative against the four examined cancer cell lines (GI50 = 1.40 μM) relative to the reference doxorubicin (GI50 = 1.20 μM), indicating the role of the oxime moiety in the
antiproliferative activity. The inhibitory impact on EGFR and BRAFV600E as potential molecular targets was
investigated for the most effective antiproliferative derivatives, 3c, 4a, and 4b. Compound 4a exhibited the
highest EGFR and BRAFV600E inhibitory activity with IC50 values of 105±10 nM and 140±12 nM, respectively,
which is comparable to the reference erlotinib with IC50 values of 80±10 nM and 60±10, respectively. Docking
computations were utilized to analyze the docking modes and scores of compounds 3c, 4a, and 4b with respect
to EGFR and BRAFV600E. The results of the docking computations revealed a favorable affinity of compound 4a
towards both EGFR and BRAFV600E, with values of -7.05 kcal/mol and -7.67 kcal/mol, respectively