In vitro cytotoxicity and docking study of novel symmetric and asymmetric dihydropyridines and pyridines as EGFR tyrosine kinase inhibitors.

Quinolines have a weighty effect as anticancer agents and 1,4-DHPs have demonstrated efficacy as anticancer agents in several studies, as well. New hybrid models of symmetric and asymmetric 1,4-DHPs and pyridines linked at C 3 of 2-chloroquinoline as a new anticancer scaffold, were designed and synthesized. Hantszch 1,4-DHPs method was adopted for chemical synthesis. MTT assay was performed for the evaluation of cytotoxicity, and EGFR tyrosine kinase assay was performed to investigate binding to our selected compounds, measured by ELISA. The IC 50 expressed in µM values revealed that compounds 4a,b, and 5i,k showed the best results against the tested four cell lines than the reference drug 5-Flurouuracil. Compound 5k displayed the most potent cytotoxic activity with IC 50  values in the low µM range (12.03 ± 1.51: 20.09 ± 2.16 µM), compared with 5-Fu IC 50 range (40.74 ± 2.46: 63.81 ± 2.69 µM). The incorporation of 2-chloroquinoline at C 3 to C 4 of 1,4-DHP could be proposed as an anticancer scaffold rather than its analogous pyridines. Ester fragments connected to 1,4-DHPs ring as a lipophilic part are essential for anticancer activity. The chirality at C 4 improved the anticancer activity. The hydrogen and halogen bond facilitated protein-ligand binding mode and affinity.