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 Moretaicang liyuan chemical co,.ltd
website:http://www.tcliyuanchem.com/productse.php
Contact:86-512-53539583
Address:Room 804,Huaxu Building,No.95,Renmin South Road,Taicang city,Jiangsu Province,China
Contact:86-21 60347964
Address:No.1304, West Meilong Road, Minhang District, Shanghai, China
Shaanxi HuaTai Bio-fine chemical company Ltd
Contact:86-029-87862197
Address:No. 5, 3rd Floor, 29 Yanta North Road, Beilin Dist.
Binzhou Holly Pharmaceutical Co.,Ltd.
Contact:74517
Address:No.15 Dapu Road,Huangpu District Shanghai,P.R.China
Weifang Adde Economic And Trade Co.,LTD.
Contact:86-536-8885548
Address:Room 1402,Wanda Plaza B Block,No.958,Yuanfei Road,Kuiwen District
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)