2. Academic Validation
  3. Synthesis of harmine-nitric oxide donor derivatives as potential antitumor agents

Synthesis of harmine-nitric oxide donor derivatives as potential antitumor agents

  • Bioorg Med Chem Lett. 2022 Jun 1;65:128698. doi: 10.1016/j.bmcl.2022.128698.
Zhezhe Li 1,  Yipaerguli Apizi 1,  Chengzhong Zhang 2,  Zhaozhi Wang 1,  Hongji He 1,  Xiaoya Li 3,  Yina Zhu 3,  Jishun Yang 4,  Liang Xiao 5,  Mei Wang 6
Affiliations

Affiliations

  • 1 College of Pharmacy, Xinjiang Medical University, Urumqi 830000, China.
  • 2 Department of Pharmacy, Naval Medical University (Second Military Medical University), Shanghai 200433, China.
  • 3 Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai 200433, China.
  • 4 Characteristic Medical Center, Naval Medical University (Second Military Medical University), Shanghai 200052, China. Electronic address: [email protected].
  • 5 Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai 200433, China. Electronic address: [email protected].
  • 6 College of Pharmacy, Xinjiang Medical University, Urumqi 830000, China. Electronic address: [email protected].
PMID: 35341920 DOI: 10.1016/j.bmcl.2022.128698
Abstract

To further improve the anti-tumor activity of Harmine (HM), we took the hybridization approach and synthesized harmine derivatives-furoxan hybrids containing nitric oxide (NO) releasing parts by connecting NO donors with anti-tumor active fragments to harmine. Then, the synthesized compounds were evaluated for their in vitro cytotoxicity against five human Cancer cell lines. Among them, compound 10 was found to have the strongest antiproliferative activity against HepG2 (IC50 = 1.79 µM). In addition, compound 10 produced high levels of NO in vitro, verifying that the release of NO was closely correlated to the antiproliferative activity. In addition, Compound 10 also showed good plasma stability. Finally, we also preliminarily investigated the acute toxicity of compound 10 in mice and assessed the absorption of compound 10 by Caco-2 cell permeability assay. In brief, the remarkable biological characteristics of the new harmine derivatives-furoxan hybrids may make them promising candidates for human Cancer intervention.

Keywords

Antitumor; Apoptosis; Derivative; Harmine; NO releasing; Synthesis.

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