Steady-state and 3D fluorescence study reveals the binding of a dicoumarol analogue in subdomain IIA of human serum albumin with structural variation

Abstract

Drugs exhibit pharmacological properties through their binding interactions with the target receptors. Coumarins and dicoumarols are known to exhibit diverse pharmacological potential. 3,3′-Carbonylbis (7-diethylamino coumarin) (CDC) is a bis-coumarin derivative with antioxidant activity. The interaction of CDC to human serum albumin (HSA) has been reported here. The fluorescence quenching of HSA by CDC at 303, 308, and 313 K revealed a dynamic quenching with a quenching constant of 104 M−1 order. The binding constant from spectroscopic methods was found to be 103 M−1 order. Thermodynamic parameters (∆S0, ∆H0, and ∆G0) were calculated from temperature studies using the Van't Hoff equation. A negative ∆G0 value showed the spontaneity of the interaction. A positive ∆S0 value and negative ∆H0 value indicated the major role of an electrostatic force. Further the binding was found to be an entropy-driven process. Site-specific marker displacement studies with 1-Anilino-8-naphthalene sulfonate (ANS), warfarin, and ibuprofen revealed CDC binding at site-1 in subdomain IIA. HSA conformational changes were verified using synchronous and 3D fluorescence studies. Secondary structural changes in HSA were visible from circular dichroism results. Molecular docking results corroborated the experimental finding showing CDC binding at site-1 in HSA.