European Journal of Medicinal Chemistry (2019)
Update date:2022-08-03
Topics:
Yin, Yong
Sha, Shao
Wu, Xun
Wang, She-Feng
Qiao, Fang
Song, Zhong-Cheng
Zhu, Hai-Liang
PI3K signal pathway plays a vital role in cellular functions and becomes an attractive approach for cancer therapy. Herein, a new series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivatives bearing sulfonylpiperazine based on the PI3K inhibitors and our previous research. They were screened for their PI3K inhibitory activities and anticancer effects in vitro. Biological studies indicated that compound 7m revealed the remarkable antiproliferative activity (IC50 ranging from 0.03 to 0.09 μM) against four cancer cell lines (A549, Huh7, HL60 and HCT-116). Besides, compound 7m displayed a certain selective for PI3Kα (IC50 = 0.009 μM) over PI3Kβ, γ and δ, and meanwhile, it can remarkable decreased the expression level of p-Akt (Ser473) and p-S6K. In addition, compound 7m could not only induce HCT-116 cell arrest at G1 phase in a dose-dependent manner, but also induce cell apoptosis via upregulation of Bax and cleaved-caspase 3/9, and downregulation of Bcl-2. Besides, compound 7m can remarkably inhibit the growth of tumor in vivo. The above results suggested that compound 7m could be considered as a promising PI3Kα inhibitor.
View MoreHebei Tianxiang Biological & Pharmaceutical Co., Ltd
Contact:86-0312-6615158
Address:No 42 fazhan street qingyuan county
CHANGZHOU HANGYU PHARMACEUTICAL TECHNOLOGY CO., LTD
website:http://www.czyys.com
Contact:0086-519-88802789
Address:No.300,Yanling Middle Road, Changzhou, Jiangsu, China
Jintan City Mego Chemical Co., Ltd
Contact:+86-0519-82814387
Address:23# Dengguan Town, Jintan, Jiangsu Province, China
Shuanghe Bio-Technology Limited(expird)
Contact:+86-571-61710758,18968016640
Address:Jinqiao north road 916# Fuyang
ANHUI CHEM-BRIGHT BIOENGINEERING CO.,LTD
Contact:86-561-4080321
Address:No.8 Lieshan Industrial Zone of Huaibei
Doi:10.1016/S0022-2860(98)00895-3
(1999)Doi:10.1016/S0008-6215(00)82943-2
(1974)Doi:10.1039/c8cc07311b
(2018)Doi:10.1016/j.tet.2016.07.007
(2016)Doi:10.1039/c5ra25176a
(2016)Doi:10.1016/j.bmcl.2006.06.048
(2006)