2. Academic Validation
  3. Novel nitric oxide-releasing spirolactone-type diterpenoid derivatives with in vitro synergistic anticancer activity as apoptosis inducer

Novel nitric oxide-releasing spirolactone-type diterpenoid derivatives with in vitro synergistic anticancer activity as apoptosis inducer

  • Bioorg Med Chem Lett. 2016 Sep 1;26(17):4191-6. doi: 10.1016/j.bmcl.2016.07.059.
Dahong Li 1,  Tong Han 1,  Kangtao Tian 1,  Shuang Tang 1,  Shengtao Xu 2,  Xu Hu 1,  Lei Wang 2,  Zhanlin Li 1,  Huiming Hua 3,  Jinyi Xu 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 Department of Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, 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. Electronic address: huimhua@163.com.
  • 4 Department of Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. Electronic address: jinyixu@china.com.
PMID: 27491707 DOI: 10.1016/j.bmcl.2016.07.059
Abstract

Herein, we reported the cytotoxicity, NO-releasing property, and Apoptosis induced ability of two series of novel nitric oxide-releasing spirolactone-type diterpenoid derivatives (10a-f and 15a-f). All the title compounds were more potent than oridonin (7) and parent compound (9 or 14) against human tumor Bel-7402, K562, MGC-803 and CaEs-17 cells. SARs were concluded based on above data. Compound 15d exhibited the strongest antiproliferative activity with the IC50 of 0.86, 1.74, 1.16 and 3.75μM, respectively, and could produce high level (above 25μM) of NO at the time point of 60min. Further mechanism evaluation showed that 15d could induce S phase cell cycle arrest and Apoptosis at low micromolar concentrations in Bel-7402 cells via mitochondria-related pathways. It was expected that the remarkable biological profile of the synthetic NO-releasing spirolactone-type diterpenoid analogs make them possible as promising candidates for the development of Anticancer agents.

Keywords

Antiproliferative; Diterpenoid; NO-releasing; Oridonin; Spirolactone-type.

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