Promising Anticancer Activity of β-Carboline Derivatives: Design, Synthesis, and Pharmacological Evaluation

beta-carboline consists of a pyridine ring fused to an indole skeleton; it possesses numerous pharmacological activities, including anticancer. Previously, we reported a satisfactory 2D and 3D QSAR study on beta-carboline derivatives. Based on QSAR studies, we designed, synthesized, characterized, and screened fourteen beta-carboline derivatives for anticancer activity. Eleven of them demonstrated potent anticancer activity against both liver (HepG2) and adenocarcinoma (A549) cell lines. Compound 1-(N, N-dimethylbenzenamine)-3-(4-(p-tolylmethanimine)-5-thio-1, 2, 4-triazol-3-yl) beta-carboline (9) was found to be most potent against both cancer cell lines and equipotent towards standard drug Adriamycin. Compounds 1-(p-tolyl)-3-(4-(p-(iminomethyl)-N, N-dimethylbenzenamine) -5-thio-1, 2, 4-triazol-3-yl) beta-carboline (4) and 1-(N, N-dimethylbenzenamine)-3-(4-(m-tolylmethanimine)-5-thio-1, 2, 4-triazol-3-yl) beta-carboline (10) were found to be 7 to 10 times less potent as compared to Adriamycin against the HepG2 cell line. Molecular docking was also performed with the Glide docking program to explore the binding mode between the synthesized beta-carboline derivatives and the receptor CDK2 [1AQ1] protein.