Analisis Kemiripan Obat, Prediksi Toksisitas dan Studi Molecular Docking Metabolit Sekunder Dari Streptomyces carpaticus Terhadap Protein Caspase-3 Sebagai Antikanker Leukemia

Adam Suduri, Huda Shalahudin Darusman, Silmi Mariya

Abstract


Caspase-3 merupakan enzim protease yang berperan dalam proses apoptosis, dan menjadi target senyawa metabolit dalam menghambat pertumbuhan sel kanker. Tujuan penelitian adalah untuk mengetahui sifat kemiripan obat metabolit sekunder hasil produksi Streptomyces carpaticus yang diperoleh berdasarkan analisis klaster gen biosintesis pada program antiSMASH version 7.1.0, mengetahui hasil prediksi mutagenicity dan toxicity serta mengetahui hasil interaksi metabolit sekunder dengan protein Caspase-3 yang merupakan reseptor terkait sel kanker leukemia menggunakan molecular docking. Hasil analisis kemiripan obat dan prediksi ADME menunjukkan bahwa ketiga metabolit memenuhi aturan Lipinski Rule of Five dan memiliki kemiripan dengan obat. Ketiga metabolit tergolong pada Toxicity Class 5, dan memiliki sifat mutagenic inactive dengan probability Pristinol: 0.93, Raimonol: 0.91 dan Cyslabdan: 0.80 dan toxicity inactive dengan probability Pristinol: 0.75, Raimonol: 0.94 dan Cyslabdan: 0.76. Hasil studi molecular docking, analisis dan validasi situs ikatan dengan protokol penambatan ulang (redocking) ligan standar 5-[4-(1-carboxymethyl-2-OXO-propylcarbamoyl)-benzylsulfamoyl]-2-Hydroxy-Benzoic Acid memiliki nilai RMSD yaitu 0.000. Energi ikatan bebas masing-masing ligan yaitu sebesar -8,9 kkal/mol -9.2 kkal/mol, -7.0 kkal/mol, -7.1 kkal/mol, dan -7.0 kkal/mol. Hasil ini menunjukan bahwa energi ikatan hasil penambatan metabolit sekunder dengan protein Caspase-3 yang paling baik adalah metabolit cyslabdan dengan nilai ikatan bebas -7.4 kkal/mol dan jumlah interaksi 12.

Keywords


Caspase-3; Kemiripan Obat; Metabolit Sekunder; Molecular Docking; Toxicity

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DOI: https://doi.org/10.37905/jambchem.v6i2.26802

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