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Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies

Zang, Yingda, Lai, Fangfang, Fu, Junmin, Li, Chuangjun, Ma, Jie, Chen, Chengjuan, Liu, Ke, Zhang, Tiantai, Chen, Xiaoguang, Zhang, Dongming·2020·European Journal of Medicinal Chemistry

Abstract

A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD 50 = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.

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Research works printed but not linked: 29

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Metadata

Authors
Zang, Y., Lai, F., Fu, J., Li, C., Ma, J., Chen, C., Liu, K., Zhang, T., Chen, X., & Zhang, D.
Venue
European Journal of Medicinal Chemistry
Publisher
Elsevier BV
Published
2020-03
Volume
190
Pages
112079
ISSN
0223-5234
Cited by
31
References
1
Language
en
Funders
  • National Natural Science Foundation of China (21572275)
  • Drug Innovation Major Project (2018ZX09711001-003, 2018ZX09735006)
  • CAMS Innovation Fund for Medical Sciences (2017-I2M-3-010, 2016-I2M-3-008)
  • Fundamental Research Funds for the Central Universities (3332018089)

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