Design, synthesis and biological evaluation of aloperine derivatives as potential anticancer agents

被引：1

作者：

Zhao, Tian-Tian ^{[1
,2
]}

Shen, Long-Ying ^{[1
,2
]}

Cheng, Yu ^{[1
,2
]}

Liu, Xiang-Ying ^{[1
,2
]}

Chen, Kai ^{[1
,2
]}

Sun, Bao-Ming ^{[3
]}

Li, Yan ^{[4
]}

Pan, Xian-Dao ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing Key Lab Act Subst Discovery & Druggabil Ev, Beijing 100050, Peoples R China

[3] Beijing Zhongke Risheng Sun Technol Co Ltd, Beijing 102600, Peoples R China

[4] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Dept Pharmacol, Beijing Key Lab New Drug Mech, Beijing 100050, Peoples R China

来源：

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH | 2024年 / 26卷 / 09期

关键词：

Aloperine; anticancer; structure-activity relationship; cell apoptosis; cell cycle arrest; CELL-CYCLE ARREST; COLORECTAL-CANCER CELLS; NATURAL-PRODUCTS; APOPTOSIS; PROLIFERATION; IDENTIFICATION; STRATEGIES; DISCOVERY; INDUCTION; VIRUS;

D O I：

10.1080/10286020.2024.2349660

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Modifications at different positions on the aloperine molecule were performed to improve its anticancer activity and develop anticancer drugs. The in vitro anticancer activities of 44 synthesized compounds were evaluated. The effect of modification positions on anticancer activity was discussed and a structure-activity relationship analysis was established. A novel series of compounds with modifications at the N12 position showed much higher cytotoxicity than aloperine. Among them, compound 22 displayed promising in vitro anticancer activity against PC9 cells with a median inhibitory concentration (IC50) of 1.43 mu M. The mechanism studies indicated that compound 22 induced cell apoptosis and cell cycle arrest in PC9 cells. These results demonstrate the potential of aloperine thiourea derivatives in anticancer activity.

引用

页码：1057 / 1086

页数：30

共 32 条

[1] Aloperine: Stereocontrolled synthesis of two stereoisomers and determination of absolute configuration [J].