Design, synthesis, and biological evaluation of 2-(naphthalen-1-yloxy)-N-phenylacetamide derivatives as TRPM4 inhibitors for the treatment of prostate cancer

被引：2

作者：

Niu, Le ^{[1
,2
,3
]}

Liu, Huina ^{[1
]}

Li, Xiaomei ^{[1
]}

Wang, Lin ^{[2
,3
]}

Hua, Hui ^{[1
]}

Cao, Qiaofeng ^{[2
,3
]}

Xiang, Qiuping ^{[1
]}

Cai, Ting ^{[1
]}

Zhu, Dongsheng ^{[2
,3
]}

机构：

[1] Ningbo 2 Hosp, Guoke Ningbo Life Sci & Hlth Ind Res Inst, Ningbo 315010, Peoples R China

[2] Nanjing Med Univ, Dept Urol, Affiliated Hosp 2, Nanjing 211166, Peoples R China

[3] Nanjing Med Univ, Sch Pharm, Dept Med Chem, Nanjing, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2024年 / 98卷

基金：

中国国家自然科学基金;

关键词：

TRPM4; Prostate cancer; Drug design; Cellular potency; NONSELECTIVE CATION CHANNEL; INCREASED SURVIVAL; ABIRATERONE;

D O I：

10.1016/j.bmc.2023.117584

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Transient receptor potential melastatin 4 (TRPM4) is considered to be a potential target for cancer and other human diseases. Herein, a series of 2-(naphthalen-1-yloxy)-N-phenylacetamide derivatives were designed and synthesized as new TRPM4 inhibitors, aiming to improve cellular potency. One of the most promising compounds, 7d (ZX08903), displayed promising antiproliferative activity against prostate cancer cell lines. 7d also suppressed colony formation and the expression of androgen receptor (AR) protein in prostate cancer cells. Furthermore, 7d can concentration-dependently induce cell apoptosis in prostate cancer cells. Collectively, these findings indicated that compound 7d may serve as a promising lead compound for further anticancer drug development.

引用

页数：8

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