title: Design, synthesis, biological evaluation, and molecular docking of novel benzopyran and phenylpyrazole derivatives as Akt inhibitors.
abstract: By inspiration of good Akt1 inhibitory and cytotoxic activity of our previously screened hits 1 and 2, a series of novel benzopyrans 3a-c, 4 and phenylpyrazoles 5a-c, 6a-b, and 7 were designed, synthesized, and biologically evaluated for their in vitro Akt1 inhibitory and cytotoxic activity. The results revealed that all of these compounds showed moderate-to-excellent antiproliferative effects against the tested cancer cell lines (i.e. HL-60, OVCAR, PC-3, and HepG2). Among them, compounds 3a and 3c exhibited preferable Akt1 inhibitory activities (IC(50) of 3a and 3c are 6.18 and 5.28 μm, respectively), while compounds 4, 5a-c, 6a-b, and 7 only showed weak Akt1 inhibitory activities. Consequently, we used molecular docking and dynamic simulation to propose a mode of binding between Akt1 and the 3c compound.
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Wenhu
authors.initials: W
authors.lastname: Zhan
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Sendong
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Medicinal Chemistry, College of Pharmaceutical Science, Zhejiang Chinese Medicinal University, Hangzhou, 310053, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Pharmacy, Zhejiang Medical College, 481 Binwen Road, Hangzhou, 310053, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Pharmacy, Zhejiang Medical College, 481 Binwen Road, Hangzhou, 310053, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Du
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D011720:Pyrazoles; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt1; benzopyran; cytotoxic activities; molecular docking; phenylpyrazole