This study evaluates the biochemical interactions between two widely used anticoagulants agents, Aspirin and Warfarin, with the Pepsin as the main stomach protease. These two drugs usually prescribe orally for long period daily use to reduce cardiovascular and thrombi death which leads to being in close contact with Pepsin. This interaction could induce related gastrointestinal problems such as peptic ulcer. In this regard, the conformational changes and enzymatic activity of the Pepsin induced by Aspirin and Warfarin were studied by using several spectroscopic methods along with molecular modeling approaches. Results confirm the formation of stable complexes between protein and drugs which leads to slight subsequent conformational changes of protein structure. The quenching mechanisms for both drug-Pepsin interactions are static. In the case of Warfarin, the hydrophobic interactions are the most important interactions. Also for Aspirin, hydrogen bond and van der Waals forces are mainly involved in the binding process. The Warfarin shows the induction of some conformational changes resulted in suppressing the protease activity and the Aspirin reversely enhanced the enzyme activity function. This study provides useful information regarding the effects of Warfarin and Aspirin on Pepsin which are helpful for the choosing of therapeutics depending on the patients' condition.
Keywords: Aspirin; Molecular dynamic simulation; Pepsin; Protein-drug interaction; Spectroscopy; Warfarin.
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