Investigation of Anti-Cancer Drug Nimustine Interaction with Calf Thymus DNA

Abstract

Nimustine, a chloroethyl nitrosourea derivative (CENU), is an antineoplastic agent, which is used for the treatment of various types of cancer. The present study focuses on the prediction and investigation of binding properties of nimustine with DNA using molecular modeling and UV–Visible spectroscopic technique. The docking study show that nimustine plausibly binds within the major groove of DNA. Further analysis of docking suggests direct interaction of nimustine with the moieties of heterocyclic nitrogenous bases of DNA. The free binding energy value of the best nimustine-DNA docked conformer is predicted as −4.31 kcal/mol using docking results.The molecular modeling study also reveals that the interaction between nimustine and DNA is majorly governed by van der Waals forces, hydrogen bonding and hydrophobic interactions, whereas the contribution of electrostatic forces stands negligible. Further, UV–Visible spectra of free calf thymus DNA and its complexes with varying concentration of nimustine indicate the binding constant (K _a ) value as 3.27 × 10³ M⁻¹, which suggests moderate interaction of nimustine with DNA. The spectroscopic results are further used to calculate the binding free energy of the complex using the relation ΔG = −RT ln (K _a ). This accounts for a value of −4.79 kcal/mol. It corroborates well with the docking outcomes. The results of present study may help in designing and synthesis of new chloroethyl nitrosourea derivatives with improved efficacy and specificity for the target molecules.