Design, synthesis and biological evaluation of 2-indolinone derivatives as PAK1 inhibitors in MDA-MB-231 cells

被引：6

作者：

Yao, Dahong ^{[1
,2
,3
]}

Ruhan, A. ^{[1
]}

Jiang, Jin ^{[1
]}

Huang, Jian ^{[1
]}

Wang, Jinhui ^{[1
]}

Han, Weina ^{[1
]}

机构：

[1] Harbin Med Univ, Coll Pharm, Dept Med Chem & Nat Med Chem, Baojian Rd 157, Harbin 150081, Peoples R China

[2] Shenzhen Technol Univ, Sch Pharmaceut Sci, Shenzhen 518118, Peoples R China

[3] Shenzhen Univ, Sch Pharmaceut Sci, Shenzhen 518118, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 17期

关键词：

PAK1; inhibitor; Breast cancer; Molecule docking; Apoptosis; Migration; P21-ACTIVATED KINASES; TARGETS;

D O I：

10.1016/j.bmcl.2020.127355

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

P21-activated kinase 1 (PAK1) plays a vital role in the proliferation, survival and migration of cancer cells, which has emerged as a promising drug target for cancer therapy. In this study, a series of 2-indolinone derivatives were designed and synthesized through a structure-based strategy. A potent PAK1 inhibitor (ZMF-005) was discovered, which presented an IC50 value of 0.22 mu M against PAK1 with potent antiproliferative activity. Furthermore, we predicted the binding mode of ZMF-005 and PAK1 by molecule docking and dynamic (MD) simulation. In addition, ZMF-005 was documented to induce significant apoptosis and suppress migration in MDA-MB-231 cells. Collectively, these findings revealed that ZMF-005 is a novel potent PAK1 inhibitor for breast cancer treatment.

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页数：8

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