Novel thienopyrimidine derivatives as dual EGFR and VEGFR-2 inhibitors: design, synthesis, anticancer activity and effect on cell cycle profile

Journal of Enzyme Inhibition and Medicinal Chemistry

Aml E.-S. Mghwary¹  Aliaa M. Kamal¹  Suzan M. Abuel-Maaty¹  Ehab M. Gedawy¹ 

[1]Cairo University

关键词: thieno[2,3-d]pyrimidines;    design;    synthesis;    anticancer activity;    egfr;    vegfr-2;    vandetanib;    apoptosis;   

DOI  :  10.1080/14756366.2019.1593160

来源: DOAJ

【 摘 要 】

Aim: Design and synthesis of thienopyrimidine derivatives as dual EGFR and VEGFR-2 inhibitors.Material and methods: A series of novel 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidine derivatives with different substituents on C-4 position was synthesized and evaluated for their anticancer activity against MCF-7 cell line. EGFR, VEGFR-2 inhibitory assay, the cell cycle analysis and apoptosis induction ability of the most potent compound 5f were evaluated.Results: Most of the compounds showed moderate to significant anticancer activity. Compound 5f exhibited the most potent anticancer activity being 1.73- and 4.64-folds more potent than erlotinib and doxorubicin, respectively. Compound 5f showed potent EGFR inhibitory activity being 1.18-folds more potent than reference standard erlotinib and it also showed good VEGFR-2 inhibitory activity at the micromolar level with IC50 value 1.23 µM. Compound 5f caused induction of cell cycle arrest at G2/M phase and accumulation of cells in pre-G1 phase. Compound 5f induced cellular apoptosis.

【 授权许可】

Unknown