evaluation of pharmacokinetic parameters, delivery, distribution and anticoagulative effects of new 4,7-dihydroxycoumarin derivative.

In this study, pharmacological profiling and investigation of the anticoagulant activity of the newly synthesized coumarin derivative: ()-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate () were performed. The obtained results were compared with the parameters obtained for Warfarin (), which is a standard good oral anticoagulant. The estimated high binding affinity of toward plasma proteins (PPS% value is > 90%) justifies the investigation of binding affinity and comparative analysis of and to Human Serum Albumin () using the spectrofluorimetric method (296, 303 and 310 K) as well as molecular docking and molecular dynamics simulations. Compound shows a very good binding affinity especially to the active site of (the active site I -subdomain IIA), quenching fluorescence by a static process. Also, the finite element smeared model (Kojic Transport Model, KTM), which includes blood vessels and tissue, was implemented to compute the convective-diffusion transport of and within the liver. Finally, compound shows a high degree of inhibitory activity toward the receptor comparable to the inhibitory activity of . Stabilization and limited flexibility of amino acid residues in the active site of the after binding of and indicates a very good inhibitory potential of compound . The high affinity of the for the enzyme (Vitamin K antagonist), as well as the structural similarity to commercial anticoagulants (), provide a basis for further studies and potential application in the treatment of venous thrombosis, pulmonary embolism and ischemic heart disease.Communicated by Ramaswamy H. Sarma.