A comparison of anticoagulant activities of warfarin and its imino-derivatives: in silico molecular docking evaluation.

Abstract

A comparison of anticoagulant activities of the enantiomers of warfarin and its imino derivatives was predicted by in silico molecular docking evaluation. The properties prediction results were calculated using the famous online server SwissADME, which showed that the studied derivatives fulfilled five Lipinski's rule of five. These results indicate that these compounds are expected to be well absorbed with good permeability and bioavailability. Furthermore, the anticoagulant activities of warfarin and its imino derivatives were investigated against vitamin K epoxide reductase using molecular docking. In this study, Molegro was the tool of choice where the new imino derivatives of warfarin have been docked within vitamin K epoxide reductase (VKOR) with PDBID: 3kp9. The docking results clearly indicated that the studied imino derivatives of warfarin have lower binding affinities, compared to warfarin with -7.4 and -8.08 kcal/mol for MNR and MAR derivatives, respectively. S-derivatives of ONS, MNS, OAS, and MAS showed to lower binding affinities with values of -5.65, -6.22, -5.26, -5.41 kcal/mole for ONS, MNS, OAS, MAS, respectively. Thus, all the studied ligands showed lower rerank scores ranged from -85.677 to -109.374, which indicated their stable bonds toward VKOR and higher biological activity. Overall, the MAR-VKOR complex was more potent derivative with a lower rerank score of -106.721 and binding affinity -8.08 kcal/mol respectively. The derivatives have shown both H bonds and steric interactions with the protein amino acids, which reflect their ability to be promiscuous the drug candidates. These findings are important to pan the experimental results for the imino derivatives.