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 BRAFV600E 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 BRAFV600E kinases. Compounds 7b, 9b, and 9d displayed the highest binding affinities and similar binding pattern to those of erlotinib.
['Mohassab|Aliaa M|AM|', 'Hassan|Heba A|HA|', 'Abdelhamid|Dalia|D|', 'Gouda|Ahmed M|AM|', 'Youssif|Bahaa G M|BGM|', 'Tateishi|Hiroshi|H|', 'Fujita|Mikako|M|', 'Otsuka|Masami|M|', 'Abdel-Aziz|Mohamed|M|']
D000970:Antineoplastic Agents D017209:Apoptosis D002460:Cell Line D049109:Cell Proliferation D002599:Chalcone D004305:Dose-Response Relationship, Drug D015195:Drug Design D004354:Drug Screening Assays, Antitumor D066246:ErbB Receptors D006801:Humans D015394:Molecular Structure D047428:Protein Kinase Inhibitors D048493:Proto-Oncogene Proteins B-raf D011804:Quinolines D013329:Structure-Activity Relationship D014230:Triazoles
Quinoline EGFR Chalcone Docking Apoptosis BRAF(V600E) Triazole