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

Abstract

Despite burgeoned knowledge about the origin, growth, tissue interactions, and spread of cancer in recent years, the functional complexity and unique survival ability of cancer cells still make it difficult to target them. Riviciclib is a semi-synthetic derivative of rohitukine and possesses anticancer potential. Inhibition of nucleic acid activity in an uncontrolled dividing cell can form the basis for the development of new-age cancer therapeutics. The present study reports the molecular interaction between riviciclib and nucleic acid (DNA/tRNA) using spectroscopic and molecular docking studies in an attempt to comprehend its cellular toxicity as well as the nature and mode of binding between them. Vibrational spectroscopic results suggest that riviciclib intercalates DNA duplex and primarily binds with guanine, adenine, and thymine nucleobases. While in the case of riviciclib-tRNA complexation, riviciclib interacts mostly with uracil residues of the tRNA molecule. Besides nucleobases, riviciclib interacts with the sugar-phosphate backbone of both biomacromolecules. Conformationally, DNA alters from B-form to C-form, whereas tRNA shows no change in its native A-form. The order (104 M−1) of binding constant for riviciclib-nucleic acid complexation infer moderate to strong affinity of riviciclib with DNA and tRNA, respectively. Molecular docking explorations are further in corroboration with our spectroscopic outcomes.