Investigation of Interactions between Thrombin and Ten Phenolic Compounds by Affinity Capillary Electrophoresis and Molecular Docking

Abstract

Thrombin plays a vital role in blood coagulation, which is a key process involved in thrombosis by promoting platelet aggregation and converting fibrinogen to form the fibrin clot. In the receptor concept, drugs produce their therapeutic effects via interactions with the targets. Therefore, investigation of interaction between thrombin and small molecules is important to find out the potential thrombin inhibitor. In this study, affinity capillary electrophoresis (ACE) and in silico molecular docking methods were developed to study the interaction between thrombin and ten phenolic compounds (p-hydroxybenzoic acid, protocatechuic acid, vanillic acid, gallic acid, catechin, epicatechin, dihydroquercetin, naringenin, apigenin, and baicalein). The ACE results showed that gallic acids and six flavonoid compounds had relative strong interactions with thrombin. In addition, the docking results indicated that all of optimal conformations of the six flavonoid compounds were positioned into the thrombin activity centre and had interaction with the HIS57 or SER195 which was the key residue to bind thrombin inhibitors such as argatroban. Herein, these six flavonoid compounds might have the potential of thrombin inhibition activity. In addition, the developed method in this study can be further applied to study the interactions of other molecules with thrombin.

The Effects of Sorbus aucuparia L. Fruit Extracts on Oxidative/Nitrative Modifications of Human Fibrinogen, Impact on Enzymatic Properties of Thrombin, and Hyaluronidase Activity In Vitro

“…The ability to inhibit the thrombin proteolytic activity was previously reported, e.g., for the polyphenol-rich chokeberry and grape seeds extracts [ 39 ], the bufadienolide-rich Kalanchoe daigremontiana root fraction [ 40 ], and the alkaloid and phenolic-rich Uncaria tomentosa leaf and bark extracts [ 15 ]. Moreover, different types of plant constituents have been investigated as potential thrombin inhibitors, including various types of polyphenols [ 41 ], and the relationship between the structure of the compounds and their activity has been examined [ 15 , 42 , 43 ]. Based on molecular docking studies, it has been established that polyphenols might be either direct or indirect thrombin inhibitors [ 15 ].…”

Characterization of Bio-active Compounds Essential for Blood Coagulation in the Crude Extracts of Tradescantia zebrina, Tagetes minuta and Codiaeum variegatum Leaves

“…This study also showed all three test samples to contain phenolic compounds. Further research by Li et al, [40] has shown that interaction between polyphenols (including tannins and flavonoids) prolongs the interaction between thrombin and these compounds. These effect leads to increased thrombin times for efficient blood coagulants.…”

Capillary electrophoresis in phytochemical analysis (2014–2017)

“…ACE method was developed in another report for binding studies of the 5‐ and 7‐hydroxyflavone (5HF and 7HF) extracted from the plant Alfalfa with serum albumin . Furthermore, ACE and in silico molecular docking methods were developed by us to study the interaction between THR and ten phenolic compounds . The results indicated that gallic acids and six flavonoids (baicalein, apigenin, naringenin, dihydroquercetin, catechin and epicatechin) had relative strong interactions with THR, and the affinity was positively correlated with the number of OH groups in A‐ring.…”