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

• Published in: Bioorganic chemistry Vol. 106; p. 104510
• Main Authors: Mohassab, Aliaa M., Hassan, Heba A., Abdelhamid, Dalia, Gouda, Ahmed M., Youssif, Bahaa G.M., Tateishi, Hiroshi, Fujita, Mikako, Otsuka, Masami, Abdel-Aziz, Mohamed
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.01.2021
• Subjects: Apoptosis; BRAFV600E; Chalcone; Docking; EGFR; Quinoline; Triazole; Triazole; BRAFV600E; Quinoline; Docking; Chalcone; EGFR; Apoptosis
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.104510

[Display omitted] •A series of quinoline/chalcone/1,2,4-triazole hybrids was synthesized and tested by NCI for their anticancer activity.•7b, 7d, 9b, and 9d were the most active compounds in most cancer cell lines with a growth inhibition between 77 and 94%.•In vitro antiproliferative activity of the new hybrids was evaluated using MTT assay.•Compounds 7a, 7b, 9a, 9b, and 9d showed promising antiproliferative activities and were evaluated against EGFR and BRAFV600E.•A docking study of compounds 7a, 7b, 9a, 9b, and 9d showed good binding affinities towards EGFR and BRAFV600E. 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.