Double-component diazeniumdiolate derivatives as anti-cancer agents

Xun Ji, Qi Chen, Viswanath Arutla, Omar Khdour, Qiong Ying Hu, Shengxi Chen

Research output: Contribution to journalArticle

Abstract

In this study, we synthesized a series of double-component O2-aryl diazeniumdiolate (DDNO) derivatives, of which each molecule can release up to four nitric oxide molecules. These compounds showed cytotoxic activities to cancer cells, such as human leukemia, breast cancer and lung cancer. Among them, compound 1 (DDNO-1) showed the highest specific activity to human leukemia cells. It induced cell apopotosis and arrest cell cycle of G2/M phase. The JNK and p38 protein kinases were activated by compound 1 to induce cancer cell apoptosis. Compound 1 also increased pro-apoptotic Bax level, which is a same function compared to a reported NO donor, JS-K. More interestingly, it decreased the level of an anti-apoptotic member Bcl-2, which is an opposite effect compared to JS-K. Compound 1 could be developed as a new anti-cancer agent since it increases the Bax/Bcl-2 ratio to overcome the drug resistance.

Original languageEnglish (US)
Article number115405
JournalBioorganic and Medicinal Chemistry
Volume28
Issue number8
DOIs
StatePublished - Apr 15 2020

Keywords

  • Anti-cancer agent
  • Bcl-2 inhibitor
  • Diazeniumdiolate derivatives
  • G2/M phase arrest
  • Leukemia
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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