Theoretical perspectives on the interaction between warfarin and garlic compounds with an in silico study of CYP3A4

• Autor(a) principal: Saldanha, Geovane de Almeida
• Data de Publicação: 2019
• Outros Autores: Bairros, André Valle de, Paula, Fávero Reisdorfer
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Saúde (Santa Maria)
• Texto Completo: https://periodicos.ufsm.br/revistasaude/article/view/36133
• topic: S-allyl-L-cysteine; S-methyl-L-cysteine; S-allylmercaptocysteine; Allium sativum L.; warfarin; CYP3A4; S-alil-L-cisteína; S-metil-L-cisteína; S-alilmercaptocisteína; Allium sativum L.; varfarina; CYP3A4

Garlic (Allium sativum L.) is one of the most consumed food supplements in the world and has multiple biological properties. Among all molecules obtained from garlic, S-allyl-L-cysteine (SAC), S-methyl-L-cysteine (SMC) and S-allylmercaptocysteine (SAMC) are highlighted. There are in vitro and in vivo studies which correlate the interactions of these molecules with medicinal drugs such as warfarin by competition site in the cytochrome P450 isoenzymes (CYP). Warfarin is an oral anticoagulant belong to vitamin K antagonist class and metabolized by CYP 3A4, 2C9 and 2C19. This article consists in a review showing studies with extracts and/or isolated garlic compounds, metabolic pathways and biological consequences considering drug interactions. The results revealed that garlic extracts express an inhibitory activity in CYP 3A4, 2C9 and 2C19. Inhibition of CYP3A4 were greater than 50% for SAC and SAMC. In silico experiment was performed for SAC, SMC and SAMC in the CYP3A4 isoenzyme which SAMC showed lower energy of interaction (-85.9 Kcal mole-1). (R)-warfarin was docked in same molecular cavity from this active site and showed lower value of energy interaction (-101.1 Kcal mole-1) in comparison with three compounds, which may suggest the warfarin showed better affinity with CYP3A4. Consequently, SAMC interacts better with CYP3A4, followed by SAC and SMC (-80.4 and -70.2 Kcal mole-1, respectively). These results indicate the mercaptocysteine shows better fit with the active site of human CYP3A4. So, these interactions may potentiate the risk of bleeding in patients during warfarin therapy, because some of the garlic compounds inhibit the CYP enzymes responsible for the biotransformation of (R)-warfarin. These findings suggest the consume of garlic should be monitored in patients receiving warfarin therapy and health professionals must be aware of this interaction.