Studi In Silico Metabolit Sekunder Kapang Monascus sp. sebagai Kandidat Obat Antikolesterol dan Antikanker - Marlia Singgih; Benny Permana; Selvira Anandia Intan Maulidya; Anna Yuliana (ALCHEMY Jurnal Penelitian Kimia, 2019)
Kapang Monascus sp. secara tradisional telah digunakan dalam fermentasi beras merah (angkak) yang bermanfaat sebagai pewarna makanan, pengawet makanan maupun obat-obatan. Saat ini, beras angkak telah menjadi suplemen makanan yang terkenal karena banyaknya senyawa bioaktif yang terkandung seperti monakolin, pigmen, asam dimerumat dan lain-lain. Tujuan penelitian ini adalah untuk menemukan metabolit sekunder kapang Monascus sp. yang meliputi senyawa monakolin dengan efek antikolesterol, pigmen dengan efek antikanker pada kanker payudara serta memprediksi toksisitas senyawa melalui studi in silico. Senyawa uji terdiri dari 14 senyawa monakolin dan 33 pigmen Monascus sp. Protein HMG KoA (3-hidroksi-3-metilglutaril koenzim A) reduktase digunakan sebagai reseptor antikolesterol sementara estrogen alfa, estrogen beta, dan aromatase digunakan sebagai reseptor antikanker. Perangkat lunak AutoDock digunakan untuk menganalisis kompleks struktural reseptor dengan senyawa uji. Prediksi toksisitas dilakukan menggunakan perangkat lunak ADMET predictor dan QSAR Toolbox. Prediksi toksisitas dan hasil docking menunjukkan bahwa asam monakolin L menunjukkan aktivitas antikolesterol yang baik terhadap HMG KoA reduktase; pigmen monaskin menunjukkan aktivitas antikanker yang selektif terhadap reseptor estrogen beta; dan keduanya diprediksi aman. Prediksi toksisitas senyawa monakolin dan pigmen Monascus sp. menunjukkan terdapat 7 senyawa monakolin yaitu 3-hidroksi-3,5-dihidromonakolin L, asam dihidromonakolin L, monakolin L, asam monakolin J, monakolin J, asam monakolin L , monakolin M, dan 5 pigmen Monascus sp. yaitu ankaflavin, monaskin, monaskopiridin A, monaskopiridin B dan monascuspiloin yang dinyatakan tidak toksik. Tujuh pigmen Monascus sp. yang terdiri dari monankarin A, monankarin B, monankarin C, monankarin D, monankarin E, monankarin F, dan monasfluol A bersifat positif mutagen, karsinogen dan toksik terhadap reproduksi. Hasil penelitian ini berpotensi dapat diaplikasikan untuk desain dan pengembangan obat antikolesterol dan antikanker.In Silico Study of Secondary Metabolites of Monascus sp. as A Candidate for Anticholesterol and Anticancer Drugs. The fungus Monascus sp. has traditionally been used to prepare red fermented rice (angkak) as a natural food colorant, food preservative or medicinal agent. Recently, it has become a popular dietary supplement due to many of its bioactive constituents such as monacolin compounds, pigments, and dimerumic acid, etc. These functional constituents also had been deemed to be provided with various health benefits. This research aims to find secondary metabolites of monacolin compounds with antihypercholesterolemic effect, Monascus sp. pigment with anticancer effect on breast cancer, and predict their toxicity through in silico study. The studied compounds consist of 14 monacolin compounds and 33 Monascus sp. pigments. HMG CoA (3-hydroxy-3-methylglutaryl Coenzyme A) reductase protein was used as antihypercholesterolemic receptor in which estrogen alfa, estrogen beta, and aromatase were used as anticancer receptors. AutoDock docking software was used to analyze structural complexes of the receptors with studied compounds. Toxicity prediction was done using ADMET predictor and QSAR Toolbox softwares. Toxicity prediction and docking results revealed that monacolin L acid exhibits good anticholesterol activity towards HMG CoA reductase; monascin pigment exhibits selective anticancer activity towards estrogen beta receptor; and both of them were predicted to be safe. Toxicity prediction of studied compounds showed that 7 monacolin compounds which are 3-hydroxy-3,5-dihydromonakolin L, dihydromonacolin L acid, monacolin L, monacolin J acid, monacolin J, monacolin L acid, monacolin M and 5 Monascus sp. pigments which are ankaflavin, monascin, monascopyridine A, monascopyridine B dan monascuspiloin are not toxic. Seven Monascus sp. pigments which are monankarin A, monankarin B, monankarin C, monankarin D, monankarin E, monankarin F and monasfluol A are mutagenic, carcinogenic and also reprotoxic. The research results could be useful for the design and development of the anticholesterol and anticancer drugs.