Synthesis, Antioxidant and Antiproliferative Actions of 4-(1,2,3-Triazol-1-yl)quinolin-2(1)-ones as Multi-Target Inhibitors.

The reaction of 4-azido-quinolin-2(1)-ones - with the active methylene compounds pentane-2,4-dione (), 1,3-diphenylpropane-1,3-dione (), and KCO was investigated in this study. This approach afforded 4-(1,2,3-triazol-1-yl)quinolin-2(1)-ones - in high yields and purity. All newly synthesized products' structures were identified. Compounds - were tested for antiproliferative activity against a panel of four cancer cell lines. In comparison to the reference erlotinib (GI = 33), compounds - were the most potent derivatives, with GI values ranging from 22 nM to 31 nM. The most effective antiproliferative derivatives, -, were subsequently investigated as possible multi-target inhibitors of EGFR, BRAF, and EGFR. Compound was the most potent inhibitor of the studied molecular targets, with IC values of 57 nM, 68 nM, and 9.70 nM, respectively. The apoptotic assay results demonstrated that compounds and function as caspase-3, 8, and Bax activators as well as down-regulators of the antiapoptotic Bcl2, and hence can be classified as apoptotic inducers. Finally, compounds and displayed promising antioxidant activity at 10 µM, with DPPH radical scavenging of 70.6% and 73.5%, respectively, compared to Trolox (77.6%).