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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
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Double-component diazeniumdiolate derivatives as anti-cancer agents
Xun Ji1, Qi Chen2, Viswanath Arutla1
1Biodesign Center for BioEnergetics, Arizona State University, Tempe, AZ 85287, USA.
Bioorganic & Medicinal Chemistry
|March 12, 2020
Summary
New nitric oxide-releasing compounds (DDNOs) show potent anti-cancer activity, particularly against leukemia. Compound 1 induces apoptosis and overcomes drug resistance by modulating Bax and Bcl-2 levels.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Pharmacology
Background:
- Nitric oxide (NO) donors are investigated for cancer therapy.
- Developing novel compounds with controlled NO release is crucial.
- Understanding mechanisms of action in cancer cells is essential.
Purpose of the Study:
- Synthesize and evaluate novel O2-aryl diazeniumdiolate (DDNO) derivatives as potential anti-cancer agents.
- Investigate the specific activity and mechanism of action of DDNO derivatives, particularly compound 1, against various cancer cell lines.
- Assess the potential of compound 1 to overcome drug resistance in cancer treatment.
Main Methods:
- Synthesis of a series of DDNO derivatives.
- In vitro cytotoxicity assays against human leukemia, breast, and lung cancer cell lines.
- Cell cycle analysis and apoptosis assays for compound 1.
- Western blot analysis to determine the levels of apoptosis-related proteins (Bax, Bcl-2) and activated kinases (JNK, p38).
Main Results:
- Synthesized DDNO derivatives demonstrated cytotoxic effects on multiple cancer cell lines.
- Compound 1 exhibited the highest specific activity against human leukemia cells.
- Compound 1 induced cancer cell apoptosis and G2/M cell cycle arrest.
- Activation of JNK and p38 kinases was observed, along with increased Bax and decreased Bcl-2 levels, leading to an elevated Bax/Bcl-2 ratio.
Conclusions:
- Compound 1, a novel DDNO derivative, effectively induces apoptosis in leukemia cells via JNK/p38 activation and modulation of Bax/Bcl-2.
- The ability of compound 1 to increase the Bax/Bcl-2 ratio suggests potential for overcoming drug resistance.
- DDNO derivatives, exemplified by compound 1, represent promising candidates for developing new anti-cancer therapeutics.
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