Uji In Silico Aktivitas Senyawa Kumarin Turunannya Terhadap Enzim Alfa Glukosidase Antidiabetes
DOI:
https://doi.org/10.29313/jrf.v3i1.2343Keywords:
Diabetes mellitus, Kumarin, Alpukat (Persea americana Mill.)Abstract
Abstract. Alpha glucosidase enzyme is one of the treatment targets for diabetes mellitus. Coumarin compounds contained in the avocado plant (Persea americana Mill.). known to have antidiabetic effects in vitro. These compounds are thought to have antidiabetic effects in vitro. This compound is thought to have an antidiabetic effect by inhibiting the alpha glucosidase enzyme, but this hypothesis has not been proven. Therefore, this study tested coumarin compounds and their derivatives, namely umbelliferone, scoparon, scopaletin, fraxetin, esculin, osthole, psoralen, rutamarin, decursinol, decursidin, edgeworin, daphnoretin, and edgeworoside c, against the alpha-glucosidase enzyme receptor using molecular docking. in silico. This study aims to determine the physicochemical parameters, affinity, and toxicity of compounds with the most potential as antidiabetics. Parameters carried out identified the physicochemical properties of the test compounds using SwissADME software and Scibio-iitd.res.in. Then macromolecular preparation was carried out using the BIOVIA Discovery Studio 2021 software. Next, the docking method was validated and the docking method simulated using the MGLTools 1.5.6 software with AutoDock Tools 4.2. The results obtained using molecular docking were then visualized using the BIOVIA Discovery Studio 2021 software. The toxicity test was carried out using Toxtree version 3.1.0. The physico-chemical parameters show that the lipophilicity, molecular weight, molar reactivity, and hydrogen bonds show that coumarin compounds and their derivatives meet the requirements of Lipinski's Rule of Five, which means that these compounds are predicted to be absorbed and can bind to target receptors. The results of molecular docking of coumarin compounds and their derivatives have an affinity for alpha glucosidase receptors. The compound that has the best affinity is edgeworoside c with a bond free energy value of -8.91 kcal/mol and an inhibition constant of 0.29255 μmolar. The toxicity results obtained were that all the tested compounds were included in the toxicity class III, which means that at high concentrations safety in use is not guaranteed. Then all coumarin test compounds and their derivatives were neither carcinogenic nor mutagenic.
Abstrak. Enzim alfa glukosidase adalah salah satu target pengobatan diabetes mellitus. Senyawa Kumarin yang terkandung dalam tanaman alpukat (Persea americana Mill.). diketahuo memiliki efek antidiabetes secara in vitro. Senyawa ini diperkirakan memiliki efek antidiabetes secara in vitro. Senyawa ini diperkirakan memiliki efek antidiabetes dengan menghambat enzim alfa glukosidase, namun hipotesa ini belum dibuktikan. Maka, penelitian ini dilakukan pengujian senyawa kumarin dan turunannya yaitu senyawa umbelliferone, scoparon, scopaletin, fraxetin, esculin, osthole, psoralen, rutamarin, decursinol, decursidin, edgeworin, daphnoretin, dan edgeworoside c, terhadap reseptor ezim alfa gkukosidase dengan menggunakan molecular docking secara in silico. Peneltian ini bertujuan untuk mengetahui parameter fisikokimia, afinitas, dan toksisitas senyawa yang paling berpotensi sebagai antidiabetes. Parameter yang dilakukan mengidentifikasi sifat fisikokimia senyawa uji menggunakan software SwissADME dan Scibio-iitd.res.in. kemudian dilakukan Preparasi makromolekul menggunakan software BIOVIA Discovery Studio 2021. Selanjutnya, dilakukan validasi metode docking dan simulasi metode docking dengan software MGLTools 1.5.6 dengan AutoDock Tools 4.2. Hasil yang diperoleh menggunakan molecular docking kemudian divisualisasikan dengan menggunakan software BIOVIA Discovery Studio 2021. Uji toksisitas dilakukan menggunakan Toxtree versi 3.1.0. Pada parameter fisiko kimia menunjukan bahwa lipofilisitas, berat molekul, reaktivitas molar, dan ikatan hidrogen bahwa senyawa kumarin dan turunanya memenuhi persyaratan Lipinski’s Rule of Five yang artinya senyawa tersebut diprediksi dapat diabsorpsi dan dapat berikatan dengan reseptor target. Hasil penambatan molekular dari senyawa kumarin dan turunannya memiliki afinitas terhadap reseptor alfa glukosidase. Senyawa yang memiliki afinitas paling baik yaitu senyawa edgeworoside c dengan nilai energi bebas ikatan -8,91 kkal/mol dan konstanta inhibisi 0,29255 μmolar. Hasil toksisitas yang diperoleh adalah seluruh senyawa uji termasuk ke dalam toksisitas kelas III yang artinya pada konsentrasi yang tinggi tidak dijamin keamanan dalam penggunaannya. Kemudian seluruh senyawa uji kumarin dan turunnya tidak bersifat karsinogenik maupun mutagenik.
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