Antiproliferative activity and apoptosis inducing effects of nitric oxide donating derivatives of evodiamine

被引:41
作者
Zhao, Nan [1 ,2 ]
Tian, Kang-tao [1 ,2 ]
Cheng, Ke-guang [3 ,4 ]
Han, Tong [1 ,2 ]
Hu, Xu [1 ,2 ]
Li, Da-Hong [1 ,2 ,3 ,4 ]
Li, Zhan-lin [1 ,2 ]
Hua, Hui-ming [1 ,2 ]
机构
[1] Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drug Design & Discovery, 103 Wenhua Rd, Shenyang 110016, Peoples R China
[2] Shenyang Pharmaceut Univ, Sch Tradit Chinese Mat Med, 103 Wenhua Rd, Shenyang 110016, Peoples R China
[3] Guangxi Normal Univ, State Key Lab Chem & Mol Engn Med Resources, 15 Yucai Rd, Guilin 541004, Peoples R China
[4] Guangxi Normal Univ, Sch Pharm & Chem, 15 Yucai Rd, Guilin 541004, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
Nitric oxide; Evodiamine; Antiproliferative activity; Apoptosis; CANCER-CELL-LINES; POTENTIAL ANTITUMOR AGENTS; BIOLOGICAL EVALUATION; IN-VITRO; BREAST-CANCER; DITERPENOID ANALOGS; HIGHLY POTENT; COLON-CANCER; LUNG-CANCER; TUMOR-CELLS;
D O I
10.1016/j.bmc.2016.05.001
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
The first series of nitric oxide donating derivatives of evodiamine were designed and prepared. NO releasing ability of all target derivatives was evaluated in BGC-823, Bel-7402 and L-02 cells. The cytotoxicity was evaluated against three human tumor cell lines (Bel-7402, A549 and BGC-823) and normal human liver cells L-02. The nitrate derivatives 11a and 11b only exhibited moderate activity and furoxan-based derivatives 13a-c, 14a and 14b showed promising activity. 13c showed good cytotoxic selectivity between tumor and normal liver cells and was further investigated for its apoptotic properties on human hepatocarcinoma Bel-7402 cells. The molecular mode of action revealed that 13c caused cell-cycle arrest at S phase and induced apoptosis in Bel-7402 cells through mitochondria-related caspase-dependent pathways. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2971 / 2978
页数:8
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