Nucleic acid binding mechanism of flavone derivative, riviciclib: Structural analysis to unveil anticancer potential

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Cancer cells exhibit complex survival mechanisms, hindering targeted therapies.
• Riviciclib, derived from rohitukine, shows promise as an anticancer agent.
• Targeting nucleic acid activity offers a strategy for novel cancer therapeutics.

Purpose of the Study:

• To investigate the molecular interactions between riviciclib and nucleic acids (DNA and tRNA).
• To elucidate the binding mode, affinity, and conformational changes induced by riviciclib.
• To understand the basis for riviciclib's potential anticancer activity and cellular toxicity.

Main Methods:

• Spectroscopic techniques (e.g., vibrational spectroscopy) were employed to study riviciclib-nucleic acid complexes.
• Molecular docking simulations were performed to predict binding interactions.
• Binding constants and conformational analyses were conducted.

Main Results:

• Riviciclib intercalates into DNA, primarily binding to guanine, adenine, and thymine.
• Riviciclib interacts with uracil residues in tRNA and the sugar-phosphate backbone of both DNA and tRNA.
• DNA undergoes a conformational change from B-form to C-form upon binding with riviciclib.
• Binding constants indicate moderate to strong affinity between riviciclib and nucleic acids.
• Spectroscopic and docking results were consistent.

Conclusions:

• Riviciclib exhibits significant molecular interactions with DNA and tRNA, suggesting a mechanism for its anticancer effects.
• The binding mode and affinity provide a foundation for understanding riviciclib's therapeutic potential.
• Further research into riviciclib's cellular effects is warranted based on these molecular insights.