PREDICTION OF THE EFFECT OF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) IN THE CYP2C9 ON WARFARIN METABOLISM BY IN SILICO STUDY

NORISCA ALIZA PUTRIANA; TAOFIK RUSDIANA; TINA ROSTINAWATI; MOHAMMAD RIZKI AKBAR; SANDRA MEGANTARA; SABRANAH HIDAYANTI

doi:10.22159/ijap.2022.v14s5.14

Authors

NORISCA ALIZA PUTRIANA Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21, Jatinangor 45363, Indonesia
TAOFIK RUSDIANA Department of Biology Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21, Jatinangor 45363, Indonesia
TINA ROSTINAWATI Department of Biology Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21, Jatinangor 45363, Indonesia
MOHAMMAD RIZKI AKBAR Department of Cardiovascular, Faculty of Medicine, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21, Jatinangor 45363, Indonesia
SANDRA MEGANTARA Department of Analytical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21, Jatinangor 45363, Indonesia
SABRANAH HIDAYANTI Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21, Jatinangor 45363, Indonesia

DOI:

https://doi.org/10.22159/ijap.2022.v14s5.14

Keywords:

Warfarin, CYP2C9, SNPs CYP2C9, In silico, Molecular modeling, Molecular docking

Abstract

Objective: This study aimed to predict the effect of SNPs CYP2C9 s on the metabolic activity of S-warfarin in the body.

Methods: Molecular modeling was performed to obtain SNPs CYP2C9 and molecular docking was performed to predict the effect of SNPs CYP2C9 on the metabolic activity of S-warfarin.

Results: The results showed that wild-type CYP2C9 had the strongest binding affinity (∆G: -9.76 kcal/mol), indicating that wild-type CYP2C9 had the best metabolic activity compared to SNPs CYP2C9. There was a decrease in hydrogen bond formation in SNPs CYP2C9 and an increase in the distance between C7 S-warfarin and Fe-Heme in CYP2C9 SNPs when compared to wild-type CYP2C9

Conclusion: The decrease in binding affinity, decrease in hydrogen bond formation, and an increase in the distance between C7 S-warfarin and Fe-Heme on SNPs CYP2C9 indicated that SNPs CYP2C9 had decreased metabolic activity against S-warfarin which led to an increased risk of bleeding.

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