2. Academic Validation
  3. O2-(2,4-dinitrophenyl)diazeniumdiolates derivatives: Design, synthesis, cytotoxic evaluation and reversing MDR in MCF-7/ADR cells

O2-(2,4-dinitrophenyl)diazeniumdiolates derivatives: Design, synthesis, cytotoxic evaluation and reversing MDR in MCF-7/ADR cells

  • Eur J Med Chem. 2018 Jan 1:143:732-744. doi: 10.1016/j.ejmech.2017.11.081.
Qixing Li 1,  Pian Zou 1,  Jianbo Sun 2,  Li Chen 3
Affiliations

Affiliations

  • 1 Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
  • 2 Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: sjbcpu@gmail.com.
  • 3 Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: chenli627@cpu.edu.cn.
PMID: 29220794 DOI: 10.1016/j.ejmech.2017.11.081
Abstract

A series of O2-(2,4-dinitrophenyl)diazeniumdiolates derivatives were designed, synthesized and antiproliferative activities evaluated as novel nitric oxide (NO)-releasing prodrugs that could be activated by glutathione S-transferases π (GSTπ). Most of these derivatives exhibited significant antiproliferative activities compared to the reported NO-donor prodrug JS-K, among which compounds 27 and 36 had superior potency with IC50 below 1 μM. NO released amounts detection of all derivatives indicated that the antiproliferative activities were positively correlated with the levels of intracellular NO release in HCT116 cells. The most potent compound 36 exhibited improved uncatalyzed stability of GSTπ. Additionally, 36 showed remarkably multidrug resistance reversal activity which reversed multidrug resistance of adriamycin (ADR) in MCF-7/ADR cells with IC50 from 84.94 μM to 1.13 μM.

Keywords

Adriamycin; Diazeniumdiolates; JS-K; Multidrug resistance; No-Releasing.

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