Structure - Function Analysis of the Cytochromes P450, Responsible for Phenprocoumon Metabolism

  • Israel Quiroga Benemérita Universidad Autónoma de Puebla
  • Thomas Scior Benemérita Universidad Autónoma de Puebla
Keywords: CYP450, CYP2C9, Structure-Function Relationship, Molecular Mechanics, Phenprocoumon, Docking, regioselectivity


Phenprocoumon is an oral anticoagulant used for the prophylaxis and treatment of disorders due to thrombosis. However, if oral anticoagulants are not metabolized, they could exacerbate and generate clotting disorders. Phenprocoumon is metabolized by at least four hepatic enzymes members of the cytochromes P450 family; three of which are members of the same subfamily (CYP2C9, CYP2C19 and CYP2C8). Even with too many differences in their amino acid sequence and tertiary structures, CYP2C9 and CYP3A4 have the most similar metabolic activity on phenprocoumon. In this study, we were able to explain these activity similarities using force fields of molecular mechanics for geometry and energy optimization in combination with docking techniques. The results were compared to study Structure-Function Relationships (SFR) of our four target proteins (CYP2C9, CYP2C19, CYP2C8 and CYP3A4). The study and prediction of metabolism and sites of metabolisms of drugs was successfully performed using this approach.

Author Biographies

Israel Quiroga, Benemérita Universidad Autónoma de Puebla
Factulty of Chemical Sciences
Thomas Scior, Benemérita Universidad Autónoma de Puebla
Factulty of Chemical Sciences


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