Binding studies of the anti-retroviral drug, efavirenz to calf thymus DNA using spectroscopic and voltammetric techniques

• Published in: Luminescence (Chichester, England) England), 2016-02, Vol.31 (1), p.108-117
• Main Authors: Sadeghi, Marzieh, Bayat, Maryam, Cheraghi, Shekofeh, Yari, Khirollah, Heydari, Rouhollah, Dehdashtian, Sara, Shamsipur, Mojtaba
• Format: Article
• Language: English
• Subjects: Anti-Retroviral Agents - chemistry; Benzoxazines - chemistry; Binding; Binding Sites; Constants; Deoxyribonucleic acid; DNA - chemistry; dna interaction; Drugs; efavirenz; Electrochemical Techniques; Electrophoresis; Fluorescence; intercalation; Mathematical analysis; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Thermodynamics; Voltammetry
• ISSN: 1522-7235; 1522-7243
• DOI: 10.1002/bio.2931

Interactions between efavirenz (EFZ) with calf thymus DNA (CT‐DNA) were investigated in vitro under stimulated physiological conditions using multispectroscopic techniques, cyclic voltammetry viscosity measurement, and gel electrophoresis. Methylene blue and acridine orange dyes were used as spectral probes by fluorescence spectroscopy. Hypochromicity was observed in ultra‐violet (UV) absorption band of EFZ. Considerable fluorescence enhancement of EFZ was observed in the presence of increasing amounts of DNA solution and the binding constants (Kf) and corresponding numbers of binding sites (n) were calculated at different temperatures. Thermodynamic parameters including enthalpy change (ΔH) and entropy change (ΔS) were calculated to be –304.78 kJ mol–1 and –924.52 J mol–1 K–1 according to the van ’t Hoff equation, which indicated that reaction is predominantly enthalpically driven. In addition, UV/vis absorption titration of DNA bases confirmed that EFZ interacted with guanine and cytosine preferentially. Gel electrophoresis of DNA with EFZ demonstrated that EFZ also has the ability to cleave supercoiled plasmid DNA. Circular dichroism study showed stabilization of the right‐handed B form of CT‐DNA. All results suggest that EFZ interacts with CT‐DNA via an intercalative mode of binding. Copyright © 2015 John Wiley & Sons, Ltd. Research highlights The interaction of efavirenz as an anticancer and anti‐retroviral drug with calf thymus DNA (CT‐DNA) was studied using multispectroscopic methods combined with cyclic voltammetry. Hydrogen bonds and van der Waals forces play main roles in the binding of efavirenz to CT‐DNA. The drug interacted with DNA in an intercalating mode with a binding constant of 3.50 (± 0.06) × 10 4 mol –1 L.