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Studi In Silico Senyawa Ekstrak Etil Asetat Dari Daun Bandotan (Ageratum Conyzoides L.)sebagai Antibakteri Melalui Mekanisme Inhibisi Enzim FabI
ABSTRAK
Enzim FabI berperan penting dalam dalam kehidupan bakteri karena berfungsi sebagai biokatalis dalam biosintesis asam lemak bakteri. Peran Enoyl-acyl carrier protein reductase (FabI) sebagai protein target dari senyawa asam lemak sebagai antibakteri sudah terbukti secara in vitro. Beberapa senyawa yang berasal dari ekstrak etil asetat daun Bandotan (Ageratum conyzoide L.) sudah terbukti memiliki aktivitas antibakteri, tapi mekanisme antibakterinya belum diketahui. Senyawa hasil ekstrak etil asetat daun Bandotan berupa asam heksadekanoat/asam palmitat, asam 9,12-oktadekadienoat/asam linoleat, metil-5,11,14,17-eikosatetraenoat, kumarin, 2H-1-benzopyra- 6,7-dimetoksi-2,2-dimetil-ageratokromen/ prekosen II, dan 7-metoksi-2,2-dimetil-6-vinil-2H kromen Pada penelitian ini telah dilakukan studi dan prediksi mekanisme antibakteri senyawa bioaktif hasil ekstrak etil asetat daun Bandotan dalam menginhibisi enzim FabI. Berdasarkan skrining in silico awal menggunakan parameter Rule of Five (RO5) Lipinski menunjukan mayoritas senyawa memenuhi parameter kecuali nilai Log P dari metil-5,11,14,17-eikosatetraenoat. Hasil docking acak menunjukkan adanya kecenderungan senyawa bioaktif menempati klaster 7 pada permukaan protein FabI. Analisis overlap antara senyawa bioaktif dengan senyawa pembanding (Triklosan) pada bakteri gram positif menunjukan bahwa senyawa asam lemak dan turunannya serta kumarin merupakan senyawa terbaik, sedangkan pada bakteri gram negatif senyawa asam linoleat dan metil-5,11,14,17-eikosatetraenoat merupakan ligan terbaik. Berdasarkan hasil docking terarah menunjukkan bahwa asam linoleat memiliki pola posisi, orientasi dan interaksi terbaik pada sisi aktif enzim FabI pada bakteri gram positif dan metil-5,11,14,17-eikosatetraenoat pada sisi aktif enzim FabI pada bakteri gram negatif. Berdasarkan nilai binding affinity-nya maka asam linoleat (-6,2 kkal/mol) dan Metil-5,11,14,17-eikosatetraenoat (-6,0 kkal/mol) memiliki kekuatan interaksi cukup kuat dengan sisi aktif enzim FabI, tapi tidak sekuat senyawa Triklosan (-8,9 dan 9,0 kkal/mol). Asam linoleat dan metil-5,11,14,17-eikosatetraenoat diprediksi memiliki potensi paling kuat sebagai antibakteri untuk bakteri Gram positif dan Gram negatif dibandingkan ligan sampel lainnya.
Kata Kunci: antibakteri, in silico, ekstrak etil asetat, bandotan, Enoyl-acyl carrier protein reductase (FabI), molecular docking
ABSTRACT
FabI enzymes play an important role in the life of bacteria because they function as biocatalysts in the biosynthesis of bacterial fatty acids. The role of Enoyl-acyl carrier protein reductase (FabI) as a target protein from fatty acid compounds as antibacterial has been proven in vitro. Several compounds derived from Bandotan leaf ethyl acetate extract (Ageratum conyzoide L.) have been shown to have antibacterial activity, but the antibacterial mechanism is unknown. Bandotan leaves ethyl acetate extract in the form of hexadecanoic acid / palmitic acid, 9,12-octadecadienoic acid / linoleic acid, methyl-5,11,14,17-eicosatetraenoate, coumarin, 2H-1-benzopyra-6,7-dimethoxy- 2,2-dimethyl-ageratokromen / prekosen II, and 7-methoxy-2,2-dimethyl-6-vinyl-2H kromen In this study a study and prediction of the antibacterial mechanism of bioactive compounds from Bandotan leaf ethyl acetate in inhibiting the FabI enzyme were carried out. . Based on the initial in silico screening using the Rule of Five (RO5) Lipinski parameter, the majority of compounds met the parameters except the Log P value of methyl-5,11,14,17-eikosatetraenoate. Random docking results showed a tendency for bioactive compounds to occupy cluster 7 on the surface of FabI proteins. The overlap analysis between bioactive compounds and comparative compounds (Triclosan) in gram-positive bacteria showed that fatty acid compounds and their derivatives and coumarins were the best compounds, whereas in gram-negative bacteria the compound linoleic acid and methyl-5,11,14,17-eicosatetraenoate were ligands best. Based on the results of directional docking, linoleic acid has the best pattern of position, orientation and interaction on the active side of the FabI enzyme in gram-positive and methyl-5,11,14,17-eicosatetraenoic bacteria on the active side of the FabI enzyme in gram-negative bacteria. Based on the binding affinity value, linoleic acid (-6.2 kcal/mol) and Methyl-5,11,14,17-eicosatetraenoate (-6.0 kcal/mol) have quite strong interaction strength with the active side of the FabI enzyme, but not as strong as the Trichlosan compound (-8.9 and 9.0 kcal/mol). Linoleic acid and methyl-5,11,14,17-eikosatetraenoate are predicted to have the strongest potential as antibacterial for Gram positive and Gram negative bacteria compared to other sample ligands.
Keywords: antibacterial, in silico, ethyl acetate extract, bandotan, Enoyl-acyl carrier protein reductase (FabI), molecular docking
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