标题：Design, synthesis, and evaluation of novel Akt1 inhibitors based on an indole scaffold
作者：Yang, Dezhi; Tong, Dongdong; Zhang, Qian; Wang, Yongtao; Sun, Jing; Zhang, Fenghe; Zhao, Guisen
作者机构：[Yang, Dezhi; Zhang, Qian; Wang, Yongtao; Zhao, Guisen] Shandong Univ, Dept Med Chem, Key Lab Chem Biol, Minist Educ,Sch Pharmaceut Sci, Jinan, Shando 更多
通讯作者：Zhao, GS;Zhang, FH
通讯作者地址：[Zhao, GS]Shandong Univ, Dept Med Chem, Key Lab Chem Biol, Minist Educ,Sch Pharmaceut Sci, Jinan, Shandong, Peoples R China;[Zhang, FH]Shandong Univ, 更多
来源：CHEMICAL BIOLOGY & DRUG DESIGN
关键词：Akt1 inhibitors; antiproliferative activity; GSK3; indole scaffold
摘要：A new series of potential Akt1 inhibitors with indole scaffold were designed and synthesized. The antiproliferative activity against PC-3 cell line and enzyme inhibitory activity against Akt1 were evaluated. Among them, some compounds showed much more potent antiproliferative activity and stronger Akt1 inhibitory activity compared to the positive control of GSK690693. In particular, compound 19b exhibited the most potent inhibitory activity against Akt1 with inhibition rate of 70.3% at a concentration of 10nm. Furthermore, compound 19b could dose dependently reduce the phosphorylation of the downstream GSK3 protein in the PC-3 cell line and displayed fivefold higher antiproliferative activity against PC-3 cell line with IC50 value of 3.1 +/- 0.1m than positive control (15.5 +/- 0.4m). Herein, compound 19b may serve as a promising lead for further optimization and development of novel Akt1 inhibitors based on an indole scaffold.