Details

Autor(en) / Beteiligte

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

Titel

Double-component diazeniumdiolate derivatives as anti-cancer agents

Ist Teil von

• Bioorganic & medicinal chemistry, 2020-04, Vol.28 (8), p.115405-115405, Article 115405

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •A series of NO derivatives containing four nitric oxide molecules were synthesized.•Compound 1 showed the highest specific activity to human leukemia cells.•It induced cell apopotosis and arrest cell cycle of G2/M phase.•The JNK, p38 and Bax protein kinases were activated by compound 1 to induce cancer cell apoptosis.•Compound 1 decreased the level of an anti-apoptotic member Bcl-2. 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.