Evaluating the Potential Blood Coagulant Activity ofCaenothus americanus Compounds: Computational Analysis using Docking, Physicochemical, and ADMET Studies

Abstract

AbstractCaenothus americanusis a common folk remedy for the treatment of wound bleeding. Certain compounds found in this plant have been shown to reduce clotting time. However, analyzing the effects of various compounds of a folk remedy is a time-consuming and expensive process, therefore, this study employed computational analyses using docking, physicochemical, and pharmacokinetic servers to identify potential clotting activity in C.americanus compounds. The ADMETlab, SwissADME web servers, Discovery Studio, and Autodock were used to study the proper binding to target proteins and predict the physicochemical and ADMET properties (adsorption, distribution, metabolism, excretion, and toxicity) of C. americanus compounds. Coagulation factors including activated factor (F) IIa, FVa, FVIIa, FVIIIa, FIXa, FXa, FXIa, FXIIa, and FXIIIa were chosen as target proteins. Docking studies revealed that malic acid, malonic acid, oxalic acid, and succinic acid were effective on coagulation factors, of which, malic acid had better binding to intrinsic pathway factors including FVIIa, FIIa, and FXIIIa (except FVIIIa), oxalic acid to FVIIIa, and malonic acid to FVa and FXa. Moreover, ADMET studies showed the safety profile of these compounds. In conclusion, carboxylic and alcoholic groups of malic acid, malonic acid, oxalic acid and succinic acid play a role in interaction with blood coagulation factors. Additionally, based on the ADMET characteristics and suitable pharmacokinetic potentials of these compounds, they can be introduced as blood coagulant candidates with fewer side effects in bleeding disorders. However, further studies are necessary to evaluate the precise components of theC. americanuswith the suability to bind coagulation factors.