KAJIAN POTENSI FLOROTANIN SARGASSUM MUTICUM SEBAGAI KANDIDAT ANTIDIABETES TIPE-2 BERDASARKAN STUDI MOLECULAR DOCKING - Siti Rohilah, - (2021)
ABSTRAK Penelitian ini bertujuan untuk menganalisis potensi senyawa florotanin Sargassum muticum sebagai kandidat antidiabetes tipe-2 berdasarkan studi molecular docking. Simulasi molecular docking dilakukan antara senyawa florotanin (pentafuhalol A, pentafuhalol B dan hidroksipentafuhalol A) terhadap enzim α-amilase, α-glukosidase, dipeptidil peptidase-IV (DPP-IV) dan glukosa-6-fosfat dehidrogenase (G6PD) dengan substrat alami dan kontrol positif inhibitor enzim sebagai pembanding. Tahapan penelitian meliputi preparasi protein, preparasi ligan, validasi metode docking, proses docking dan visualisasi hasil menggunakan AutoDock Tools 1.5.6, AutoDock Vina 1.1.2, PyMol 4.6.0 dan BIOVIA Discovery Studio Visualizer 2021. Hasil yang diperoleh menunjukkan bahwa senyawa florotanin berinteraksi dengan keempat enzim melalui beberapa interaksi diantaranya ikatan hidrogen, hidrofobik, elektrostatik, van der Waals, unfavorable, π-sulfur dan π-lone pair. Afinitas pengikatan pentafuhalol A, pentafuhalol B dan hidroksipentafuhalol A dengan α-amilase lebih tinggi daripada akarbosa dengan selisih 1,3; 2,9; dan 0,8 kkal/mol. Kompleks α-glukosidase dengan pentafuhalol A, pentafuhalol B dan hidroksipentafuhalol A lebih tinggi daripada akarbosa dengan selisih 0,5; 0,6; dan 2,2 kkal/mol. Kompleks DPP-IV dengan pentafuhalol A, pentafuhalol B dan hidroksipentafuhalol A lebih rendah daripada linagliptin dengan selisih 1,7; 1,8; dan 1,4 kkal/mol. Kompleks G6PD dengan pentafuhalol A, pentafuhalol B dan hidroksipentafuhalol A lebih rendah daripada polidatin dengan selisih 0,1 dan 2,8 kkal/mol serta lebih tinggi daripada polidatin dengan selisih 0,2 kkal/mol. Simulasi interaksi ligan-protein menunjukkan bahwa senyawa florotanin menginhibisi keempat enzim secara kompetitif. Berdasarkan hasil penelitian dapat disimpulkan bahwa senyawa florotanin Sargassum muticum berpotensi sebagai kandidat antidiabetes tipe-2. Penelitian lanjutan secara in vitro maupun in vivo sangat diperlukan untuk mendukung data simulasi yang diperoleh. Kata Kunci: antidiabetes, florotanin, inhibitor, molecular docking, Sargassum muticum ABSTRACT This study aims to analyze the potential of phlorotannin from Sargassum muticum as candidate for type-2 antidiabetic based on molecular docking studies. Molecular docking simulations were carried out between phlorotannin compounds (pentafuhalol A, pentafuhalol B, and hydroxypentafuhalol A) against α-amylase, α-glucosidase, dipeptidyl peptidase-IV (DPP-IV), and glucose-6-phosphate dehydrogenase (G6PD) and compared it with their own substrates and positive control enzyme inhibitor. The research stages include protein preparation, ligand preparation, docking method validation, docking process, and visualization using AutoDock Tools 1.5.6, AutoDock Vina 1.1.2, PyMol 4.6.0, and BIOVIA Discovery Studio Visualizer 2021. The results assigned that all targeted phlorotannin interact with the enzymed through hydrogen bonding, hydrophobic, electrostatic, van der Waals interactions, unfavorable, π-sulfur, and π-lone pair. The binding affinity of pentafuhalol A, pentafuhalol B, and hydroxypentafuhalol A with α-amylase is higher than acarbose with the free energy differences of 1.3; 2.9; and 0.8 kcal/mol. The α-glucosidase binding with pentafuhalol A, pentafuhalol B, and hydroxypentafuhalol A were higher than acarbose with the free energy differences of 0.5; 0.6; and 2.2 kcal/mol. The binding of DPP-IV with pentafuhalol A, pentafuhalol B, and hydroxypentafuhalol A were lower than linagliptin with free energy differences of 1.7; 1.8; and 1.4 kcal/mol. The G6PD complex with pentafuhalol A, pentafuhalol B, and hydroxypentafuhalol A was lower than polydatin with a difference of 0.1 and 2.8 kcal/mol, and higher than polydatin with free energy difference of 0.2 kcal/mol. The simulation of the ligand-protein interaction suggested that the phlorotannin compounds competitively inhibited the four enzymes. Based on the results of the study, it can be concluded that phlorotannin of Sargassum muticum can be used as candidate for type-2 antidiabetic. The in vitro and in vivo evaluation are required to support the simulation results. Keyword: antidiabetic, florotanin, inhibitor, molecular docking, Sargassum muticum