Molecular Docking Analysis Of Phenolic and Flavonoid Compounds from Eichhornia Crassipes for Antidiabetic Activity Through Interaction with PPAR- γ (5Y2O) and A-Glucosidase (3TOP)
DOI:
https://doi.org/10.20527/jps.v12i2.23583Keywords:
Eichhornia crassipes, Molecular docking, Antidiabetic, PPAR-γ, α-GlucosidaseAbstract
Diabetes Mellitus Tipe 2 (DMT2), ditandai dengan resistensi insulin dan hiperglikemia. Penelitian ini mengevaluasi potensi 30 senyawa golongan fenolik dan flavonoid dari Eichhornia crassipes sebagai agen antidiabetes melalui studi in silico, meliputi uji toksisitas (ToxTree 3.1.0, ProTox 3), analisis ADME (SwissADME), dan molecular docking (AutoDock 4.2.6). Struktur ligan uji diperoleh dari PubChem, sedangkan reseptor PPAR-γ (PDB ID: 5Y2O) dan α-Glukosidase (PDB ID: 3TOP) diunduh dari RCSB Protein Data Bank. Sebelum docking, analisis toksisitas dan ADME dilakukan. Hasil docking menunjukkan Tricin (flavonoid) berinteraksi baik dengan kedua reseptor dan memiliki nilai energi Gibbs -7.53 kcal/mol untuk PPAR-γ dan -5.19 kcal/mol untuk α-Glukosidase, mendekati ligan asli Pioglitazone (-10.03 kcal/mol) dan Acarbose (-6.86 kcal/mol). Interaksi ligan-reseptor Tricin melibatkan ikatan hidrogen dan kontak hidrofobik dengan residu kunci (misalnya, ARG288 dan TYR pada PPAR- γ, residu GLN1561 dan GLN1372 pada α-Glukosidase), mencerminkan interaksi ligan asli. Prediksi toksisitas mengklasifikasikan Tricin sebagai senyawa dengan risiko toksisitas rendah (Cramer Rules Kelas I, Kroes TTC). Selanjutnya, evaluasi ADME menunjukkan bahwa Tricin memenuhi Lipinski's Rule of Five, yang mengindikasikan penyerapan dan bioavailabilitas oral yang baik. Secara keseluruhan, senyawa Tricin dari E. crassipes menunjukkan potensi signifikan sebagai kandidat agen antidiabetes melalui penghambatan PPAR-γ dan α-Glukosidase yang selanjutnya memerlukan validasi dnegan pengujian in vitro dan in vivo. Kata Kunci: Eichhornia crassipes, Molecular Docking, Antidiabetic, PPAR-γ, α-Glucosidase Type 2 Diabetes Mellitus (T2DM), is characterized by insulin resistance and persistent hyperglycemia. This study investigated the antidiabetic potential of 30 phenolic and flavonoid compounds derived from Eichhornia crassipes using in silico approaches, including toxicity assessments (ToxTree 3.1.0, ProTox 3), ADME analysis (SwissADME), and molecular docking (AutoDock 4.2.6). Ligand structures were retrieved from PubChem, while PPAR-γ (5Y2O) and α-Glucosidase (3TOP) receptors were obtained from the RCSB Protein Data Bank. Toxicity and ADME analyses were conducted prior to molecular docking, which employed the Genetic Algorithm with 50 conformations. Docking results revealed that Tricin (a flavonoid) exhibited strong interactions with both receptors, with Gibbs free energy values of -7.53 kcal/mol for PPAR-γ and -5.19 kcal/mol for α-Glucosidase. These values are comparable to those of the native ligands Pioglitazone (-10.03 kcal/mol) and Acarbose (-6.86 kcal/mol). Tricin formed hydrogen bonds and hydrophobic contacts with key active site residues including, ARG288 and TYR327 in PPAR-γ, GLN1561 and GLN1372 in α-Glucosidase), mirroring the interactions of the native ligands. Toxicity predictions classified Tricin as low risk (Class I Cramer Rules, Kroes TTC). Furthermore, ADME evaluation showed that Tricin (aglycone) is fully compliant with Lipinski's Rule of Five, suggesting favorable properties for oral absorption and bioavailability. In conclusion, Tricin from E. crassipes demonstrates significant potential as an antidiabetic candidate and warrants further in vitro and in vivo validation.References
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