Analisis In Silico Aktivitas Derivat Asam Kafeat Ekinase (Echinacea purpurea (L). Moench.) terhadap Dipeptidyl Peptidase-IV

Abstract

Kasus diabetes mellitus (DM) telah menjadi masalah kesehatan global, terutama DM tipe II. Salah satu pengobatan DM tipe II yang menarik diteliti ialah inhibitor dipeptidil peptidase-IV (DPP-IV) karena perannya meningkatkan sekresi insulin dan proliferasi sel β-pankreas. Tanaman ekinase (Echinacea purpurea (L). Moench.) telah banyak dimanfaatkan sebagai obat herbal, mengandung asam kafeat dan derivatnya yang memiliki aktivitas antidiabetes. Penelitian ini bertujuan menganalisis interaksi molekuler serta hubungan struktur terhadap potensi inhibisi derivat asam kafeat ekinase terhadap aktivitas DPP-IV melalui kajian in silico menggunakan YASARA Structure. Gosogliptin (Pf2) digunakan sebagai ligan native dan sitagliptin sebagai pembanding. Ligan-ligan uji dengan potensi inhibisi tertinggi hingga terendah antara lain echinacoside, asam sikorat, cynarine, acteoside, asam klorogenat, asam kaftarat, asam isoklorogenat, dan asam kafeat. Echinacoside yang merupakan senyawa penciri ekinase menjadi ligan uji terbaik sebagai inhibitor DPP-IV dengan energi bebas ikatan -9.731 kkal/mol, namun kurang baik sebagai obat oral. Asam sikorat merupakan ligan terbaik yang dapat menjadi alternatif obat oral dalam pengobatan DM tipe II.

Diabetes mellitus case has become a global health problem, especially the type II. One of the most interesting treatments for type II DM is dipeptidyl peptidase-IV (DPP-IV) inhibitors which promote insulin secretion and proliferation pancreatic β cells. Ekinase (Echinacea purpurea (L). Moench.), which have been utilized as a herbal medication, contain caffeic acid and derivatives compound that has antidiabetic activity. This research is aimed to analyze molecular interactions and structural relationship to the inhibition potency of caffeic acid and derivatives against DPP-IV activity using docking simulation with YASARA Structure. Gosogliptin (Pf2) was used as native ligand and sitagliptin as comparator. Test ligands with the highest to lowest inhibition potency are echinacoside, chicoric acid, cynarine, acteoside, chlorogenic acid, caftaric acid, isochlorogenic acid, and caffeic acid. Echinacoside is the characteristic compound from echinacea, becomes the most potent DPP-IV inhibitor which shows -9.731 kcal/mol on affinity energy, but not recommended as oral drug. Chicoric acid is the best ligand that can be an alternative treatment as oral drug for type II of DM.