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Author Spotlight: Characterizing DNA G-Quadruplex by Bis-3-Chloropiperidine Based Chemical Mapping
Published on: May 12, 2023
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Alkyne-substituted diminazene as G-quadruplex binders with anticancer activities.
Changhao Wang1, Brandon Carter-Cooper2, Yixuan Du1
1Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
European Journal of Medicinal Chemistry
|May 2, 2016
Summary
New G-quadruplex ligands based on diminazene show promise as anticancer agents. These novel compounds selectively target cancer DNA structures, exhibiting significant activity against multiple cancer cell lines.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- Biophysics
Background:
- G-quadruplex ligands are investigated as anticancer agents, but clinical success has been limited.
- Diminazene (DMZ) exhibits high affinity for G-quadruplexes over DNA duplexes, but lacks potent anticancer activity.
Purpose of the Study:
- To develop novel G-quadruplex-interactive small molecules with improved anticancer properties.
- To investigate the structure-activity relationship of diminazene analogues for G-quadruplex targeting.
Main Methods:
- Utilized biophysical techniques including Nuclear Magnetic Resonance (NMR), FRET melting assays, and FRET competition assays.
- Synthesized and characterized monoamidine analogues of diminazene bearing alkyne substituents.
- Evaluated the in vitro and in vivo targeting of the c-MYC G-quadruplex.
Main Results:
- Monoamidine analogues of diminazene selectively bind to G-quadruplex structures.
- The lead analogues effectively targeted the c-MYC G-quadruplex both in vitro and in vivo.
- Alkyne DMZ analogues demonstrated potent anticancer activity (single-digit micromolar GI50) against ovarian, prostate, and triple-negative breast cancer cell lines.
Conclusions:
- Alkyne-substituted diminazene analogues represent a promising new class of G-quadruplex-targeting anticancer agents.
- These compounds show potential for further development into effective cancer therapeutics.
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