Design, synthesis and bioevaluation of novel prenylated chalcones derivatives as potential antitumor agents

•Novel prenylated chalcone derivatives were designed and synthesized.•C36 showed the excellent broad-spectrum cytotoxic activity, especially in K562 and LNCaP cancer cell lines.•C36 repress the growth of cancer cells through inducing apoptosis, arresting cell cycle by down-regulating PI3K/AKT pathway.•Derivative C36 may as a new potential AKT inhibitor. A series of novel prenylated chalcone derivatives with broad spectrum anticancer potential were designed and synthesized. Some of the synthesized target compounds showed potent anti-proliferative activities toward LNCaP (prostate cancer cell line), K562 (human leukemia cells), A549 (human lung carcinoma cell line) and HeLa (cervical cancer cell line) cell lines. Among of the active compounds, (E)-1-(4-(2-(diethylamino)ethoxy)-2-hydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(pyridin-3-yl)prop-2-en-1-one (C36) was directly interacted with protein kinase B (PKB), also known as AKT, significantly inhibited the pPI3K, pAKT(Ser473) protein levels to repress the growth of cancer cells by inducing apoptosis, arresting cell cycle. Our studies provide support for prenylated chalcone derivatives potential applications in cancer treatment as a potential AKT inhibitor. [Display omitted]