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

Abstract

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 10³ to 10⁴ 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

Keywords:

• Binding
• ct-DNA
• dicoumarol
• docking

Acknowledgments

Kandikonda Lavanya thanks to GITAM Deemed to be University, Hyderabad Campus for providing the research facility and GRIET Hyderabad for encouragement. The authors acknowledge the central research facility at the University of Hyderabad for extending the CD facility.

Authors’ contribution

K. Lavanya: Investigation, Draft preparation. Jagadeesan Saranya: Data curation. Anna Tanuja Safala Bodapati: Data analysis. Ragaiahgari Srinivas Reddy: Writing and Editing. Shravya Rao Madkue: Reviewing of manuscript. Bijaya Ketan Sahoo: Supervision.

Disclosure statement

The authors have nothing to declare.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.