Design and synthesis of novel quinoline/chalcone/1,2,4-triazole hybrids as potent antiproliferative agent targeting EGFR and BRAFV600E kinases

New quinoline / chalcone hybrids containing 1,2,4-triazole moiety have been designed, synthesized and their structures elucidated and confirmed by various spectroscopic techniques. The designed compounds showed moderate to good activity on different NCI 60 cell lines in a single-dose assay with a growth inhibition rate ranging from 50% to 94%. Compounds 7b, 7d, 9b, and 9d were the most active compounds in most cancer cell lines with a growth inhibition percent between 77% and 94%. Newly synthesized hybrids were evaluated for their anti-proliferative activity against a panel of four human cancer cell lines. Compounds 7a, 7b, 9a, 9b, and 9d showed promising antiproliferative activities. These compounds were further tested for their inhibitory potency against EGFR and BRAF(V600E )kinases with erlotinib as a reference drug. The molecular docking study of compounds 7a, 7b, 9a, 9b, and 9d revealed nice fitting into the active site of EGFR and BRAF(V600E) kinases. Compounds 7b, 9b, and 9d displayed the highest binding affinities and similar binding pattern to those of erlotinib.

Automated summary

A series of new quinoline/chalcone hybrids containing 1,2,4-triazole moiety were designed and synthesized in this study, showing moderate to good activity against various cancer cell lines. Some of these compounds exhibited promising antiproliferative activities and displayed high binding affinities in inhibiting EGFR and BRAF(V600E) kinases.