Identification of the HECT domain binding of indole-3-carbinol (I3C) derivatives for breast cancer therapy

被引：2

作者：

Zheng, Wenwen ^{[1
,2
]}

Shia, Zhichao ^{[1
,2
]}

Zhang, Xun ^{[3
]}

Wu, Weibin ^{[2
]}

Yuan, Zigao ^{[3
]}

Zhao, Lei ^{[4
]}

Li, Qinyuan ^{[3
]}

Qiu, Zixuan ^{[5
]}

Zhang, Cunlong ^{[2
]}

Chu, Bizhu ^{[4
]}

Liu, Zijian ^{[2
]}

Chen, Wei-Min ^{[1
]}

Jiang, Yuyang ^{[3
,4
,5
,6
]}

机构：

[1] Jinan Univ, Coll Pharm, Guangzhou 510632, Peoples R China

[2] Shenzhen Kivita Innovat Drug Discovery Inst, Shenzhen 518057, Peoples R China

[3] Tsinghua Shenzhen Int Grad Sch, State Key Lab Chem Oncogen, Guangdong Prov Key Lab Chem Biol, Shenzhen 518055, Peoples R China

[4] Shenzhen Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Shenzhen 518060, Peoples R China

[5] Shenzhen Bay Lab, Inst Biomed Hlth Technol & Engn, Shenzhen 518132, Peoples R China

[6] Tsinghua Univ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China

来源：

PHYTOCHEMISTRY LETTERS | 2023年 / 54卷

基金：

中国国家自然科学基金;

关键词：

Indole-3-carbinol; Derivatives; HECT domain; Michael acceptor; Breast cancer; UBIQUITIN LIGASE; SMALL-MOLECULE; CELLS; INHIBITORS; APOPTOSIS; NEDD4-1; DEATH; PTEN;

D O I：

10.1016/j.phytol.2023.01.002

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

We designed and synthesized a series of HECT (homologous to the E6-AP carboxyl terminus) domain binding inhibitors based on indole-3-carbinol (I3C) by structure-based rational drug design. Thermal shift and MTT assays indicated that compound A3 had a good HECT domain binding capacity and potent breast cancer cells inhibition activity, respectively. Subsequent studies showed that compound A3 inhibited proliferation and invasion, induced apoptosis and S-phase cell block. Additionally, compound A3 altered the expression of apoptosis and cell cycle related protein in MDA-MB-231 cells. Finally, computational simulation indicated the proposed binding mode of A3 with the NEDD4-1 HECT domain.

引用

页码：7 / 13

页数：7

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