2. Academic Validation
  3. Antiproliferative activity and apoptosis inducing effects of nitric oxide donating derivatives of evodiamine

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

  • Bioorg Med Chem. 2016 Jul 1;24(13):2971-2978. doi: 10.1016/j.bmc.2016.05.001.
Nan Zhao 1,  Kang-Tao Tian 1,  Ke-Guang Cheng 2,  Tong Han 1,  Xu Hu 1,  Da-Hong Li 3,  Zhan-Lin Li 1,  Hui-Ming Hua 4
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
  • 2 State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, and School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China.
  • 3 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China; State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, and School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. Electronic address: lidahong0203@163.com.
  • 4 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: huimhua@163.com.
PMID: 27178387 DOI: 10.1016/j.bmc.2016.05.001
Abstract

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.

Keywords

Antiproliferative activity; Apoptosis; Evodiamine; Nitric oxide.

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