In vitro interaction of nucleoside reverse transcriptase inhibitor, didanosine with calf-thymus DNA: Insights from spectroscopic studies

Abstract

Many antivirals interact with DNA and alter their expression profile. Thus, it is necessary to understand the binding mode. Didanosine, a nucleoside reverse transcriptase inhibitor, is used to treat HIV infection in patients with or without acquired immunodeficiency syndrome. Understanding the mechanism of interaction of this nucleoside reverse transcriptase inhibitor with DNA can prove useful in the development of a rational drug designing system. In vitro studies (UV–vis, fluorescence, and viscometry techniques) under physiological conditions (Tris–HCl buffer solutions, pH 7.4) show that didanosine drug interacts with calf-thymus DNA (ct-DNA) via partial intercalative binding mode. UV–visible spectroscopy confirmed the formation didanosine-DNA complex with a binding strength of about 1.5 × 105 M−1 thus indicating their biological worth. Dye displace experiments and viscometry confirmed that didanosine partially intercalates toward DNA molecules. Negative value of Gibb’s-free energy change revealed that the process is spontaneous. The thermodynamic parameters such as enthalpy change (ΔH) and entropy change (ΔS) showed that the acting forces between didanosine and ct-DNA mainly included hydrophobic interactions.