Biophysical insights on the interaction of anticoagulant drug dicoumarol with calf thymus-DNA: deciphering the binding mode and binding force with thermodynamics.

Autor: Lavanya K; Department of H&S (Chemistry), Gokaraju Rangaraju Institute of Engineering and Technology, Hyderabad, India.; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University Hyderabad Campus, Hyderabad, India., Saranya J; Department of H&S (Chemistry), Gokaraju Rangaraju Institute of Engineering and Technology, Hyderabad, India., Bodapati ATS; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University Hyderabad Campus, Hyderabad, India.; Chemistry Division, BS&H Department, BVRIT College of Engineering for Women, Hyderabad, India., Reddy RS; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University Hyderabad Campus, Hyderabad, India.; Department of Chemistry, B. V. Raju Institute of Technology (BVRIT), Narsapur, India., Madku SR; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University Hyderabad Campus, Hyderabad, India.; Department of Chemistry, St. Francis College for Women, Hyderabad, India., Sahoo BK; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University Hyderabad Campus, Hyderabad, India.
Jazyk: angličtina
Zdroj: Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Feb-Mar; Vol. 42 (3), pp. 1392-1403. Date of Electronic Publication: 2023 Apr 10.
DOI: 10.1080/07391102.2023.2199872
Abstrakt: The biological activity of drugs is exhibited due to their interactions with bio-receptors. Dicoumarol (DIC) is a natural hydroxycoumarin and a well-known anticoagulant. DNA is the genetic material and one of the targets of numerous drugs. The interaction of DIC with calf-thymus DNA (ct-DNA) has been studied using different biophysical techniques and docking studies. The binding constant in the order of 10 3 to 10 4 M -1 was observed from spectroscopic studies. Thermodynamic studies at 4 different temperatures revealed the spontaneity of the interaction with the entropy-driven process. Marker displacement studies with competitive markers of intercalators (ethidium bromide) and groove binders (Hoechst 33258) confirmed the groove-binding nature of DIC in DNA. The groove-binding mode of DIC was complemented by different studies like viscosity measurements, DNA melting, and the effect of KI on the binding. A minor perturbation in the DNA viscosity and no significant change in the DNA melting temperature ( T m ) after binding with DIC further confirms the groove binding mode. The effect of KI on the DIC and DIC-DNA system suggested the absence of DIC intercalation. The absence of significant electrostatic force was revealed from the ionic-strength effect study. Binding-induced conformational variation in ct-DNA was absent in circular dichroism studies. Molecular docking studies suggested the position of DIC within the minor groove of ct-DNA, covering three base pairs long. The outcome of this report may help in understanding the pharmacodynamics and pharmacokinetics of dicoumarol analogs and related molecules.Communicated by Ramaswamy H. Sarma.
Databáze: MEDLINE
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