In Silico, Electrochemical, and Spectroscopic Approaches on the Interaction of Nabumetone with Double-Stranded DNA

Nabumetone (NABU), a prodrug, has an anti-cyclooxygenase effect only after hepatic absorption and activation. It possesses analgesic, antipyretic, and anti-inflammatory effects like other NSAIDs. It is crucial to develop precise, affordable, and fast methods to detect calf thymus double-stranded deoxyribonucleic acid (ct-dsDNA) and understand its structural alterations due to active pharmaceutical substances. To quantify NABU and understand its interaction with ct-dsDNA, this study created an electrochemical biosensor. NABU’s interaction with ct-dsDNA was also revealed utilizing differential pulse voltammetry and fluorescence spectroscopy. NABU substantially interacts with ct-dsDNA, as revealed by the decreased oxidation signals of dGuo and dAde in the electrochemical experiment. NABU and ct-dsDNA binding constants (Kb) were measured at three temperatures (293, 303, and 308 K) using spectrofluorometric methods: 4.98 × 10 3 , 4.27 × 10 4 , and 1.12 × 10 5 . Quantitative analysis of thermodynamic parameters (ΔS = +36.58 cal mol −1 K −1 and ΔH = +9.46 kcal mol −1 ) for the NABU-ct-dsDNA complex revealed the significance of hydrophobic interactions. NABU-dsDNA interaction is confirmed by molecular docking. This research showed that NABU’s binding energy with ct-dsDNA is −6.2 kcal mol −1 , showing four strong intermolecular hydrogen bonds with guanine, adenine, Pi-Alkyl, and van der Waals interactions.