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

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• 作者：Nan Zhao^a ; ^&dagger ; ; Kang-tao Tian^a ; ^&dagger ; ; Ke-guang Cheng^b ; Tong Han^a ; Xu Hu^a ; Da-hong Li^a ; ^b ; ^{lidahong0203@163.com" class="auth_mail" title="E-mail the corresponding author} ; Zhan-lin Li^a ; Hui-ming Hua^a ; ^{huimhua@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Nitric oxide ; Evodiamine ; Antiproliferative activity ; Apoptosis
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 July 2016
• 年：2016
• 卷：24
• 期：13
• 页码：2971-2978
• 全文大小：1345 K

文摘

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.