Design, synthesis and apoptosis-related antiproliferative activities of chelidonine derivatives

被引：6

作者：

Huang, Xueyan ^{[1
]}

Cheng, Keguang ^{[2
,3
]}

Liu, Lilin ^{[1
]}

Hu, Xu ^{[1
]}

Gao, Xiang ^{[1
]}

Li, Haonan ^{[1
]}

Xu, Fanxing ^{[4
]}

Li, Zhanlin ^{[1
]}

Hua, Huiming ^{[1
]}

Li, Dahong ^{[1
]}

机构：

[1] Shenyang Pharmaceut Univ, Sch Tradit Chinese Mat Med, Key Lab Struct Based Drug Design & Discovery, Minist Educ, 103 Wenhua Rd, Shenyang 110016, Peoples R China

[2] Guangxi Normal Univ, State Key Lab Chem & Mol Engn Med Resources, 15 Yucai Raod, Guilin 541004, Peoples R China

[3] Guangxi Normal Univ, Sch Chem & Pharm, 15 Yucai Raod, Guilin 541004, Peoples R China

[4] Shenyang Pharmaceut Univ, Wuya Coll Innovat, 103 Wenhua Rd, Shenyang 110016, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Chelidonine; Nitric oxide; Antiproliferative; Apoptosis; NITRIC-OXIDE DONOR; CELLS IN-VITRO; MAJUS L; TUBULIN POLYMERIZATION; ANTITUMOR-ACTIVITY; GREATER CELANDINE; CANCER-CELLS; DEATH; DNA; MITOCHONDRIA;

D O I：

10.1016/j.bmcl.2019.126913

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

y To get chelidonine derivatives with enhanced antiproliferative activity and selectivity, a series of nitric oxide donating derivatives (10a-f and 11a-j) were designed, synthesized and biologically evaluated. Compared with chelidonine, these compounds exhibited lower IC50 values against human hepatoma cells HepG2, breast cancer cells MCF-7, colon cancer cells HCT-116, as well as leukemia cells K562. Compound 11j displayed the strongest antiproliferative activity with IC50 values of 3.91, 6.90, 4.36 and 1.12 mu M against the above four cells, respectively. Nevertheless, it showed an IC50 value > 40 mu M against human peripheral blood mononuclear cells (PBMCs), which demonstrated high selectivity between normal and cancer blood cells. In further mechanism studies, 11j showed the capability to induce K562 cells apoptosis, S phase cell cycle arrest and mitochondrial membrane potential disorder. Besides, 11j was found to be effective in promoting the expression of proapoptotic protein Bad and suppressing the expression of anti-apoptotic proteins Bcl-xL, catalase, survivin, claspin and clusterin.

引用

页数：8

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