Penapisan Senyawa Polifenol sebagai Inhibitor Betalaktamase dengan Penambatan Molekuler
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polifenol,
penambatan molekuler,
drug- likeness
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Abstract
Betalaktamase adalah enzim yang mengkatalisis hidrolisis antibiotik Betalaktam sehingga dapat menyebabkan resistensi antibiotik. Bakteri yang dilaporkan dapat menghasilkan enzim Betalaktamase antara lain Klebsiella pneumoniae, Escherichia coli, Enterobacter sp., Salmonella sp., Proteus sp., Serratia marcescens, Shigella dysenteriae, Pseudomonas aeruginosa, dan Burkholderia cepacia. Saat ini resistensi terhadap antibiotik golongan Betalaktam semakin meluas. Penggunaan antibiotik ini seringkali dikombinasikan dengan inhibitor Betalaktamase seperti asam klavulanat, sulbaktam, dan tazobaktam untuk meningkatkan efisiensi terapi. Antibiotik betalaktam adalah antibiotik spektrum luas yang banyak menjadi pilihan untuk terapi. Oleh karena itu, pencarian kandidat inhibitor Betalaktamase untuk mencegah resistensi perlu dilakukan. Pada penelitian ini dilakukan penapisan senyawa polifenol sebagai inhibitor enzim Betalaktamase dengan metode penambatan molekuler. enapisan terhadap 112 senyawa polifenol dari database menghasilkan 27 senyawa yang memiliki energi bebas ikatan yang lebih baik dari ligan alami. Prediksi drug-likeness berdasarkan aturan Lipinski terhadap 27 senyawa tersebut menghasilkan 6 senyawa yang berpotensi, yaitu trans-resveratrol 3-O-glucuronide, apigenin-7-O-glucoside, cis-resveratrol 4'-sulfate, sulfuretin, dan apigenin. Berdasarkan visualisasi interaksi ligan-reseptor, keenam senyawa tersebut berinteraksi dengan residu katalitik enzim betalaktamase. Energi bebas ikatan terbaik ditunjukkan oleh trans-resveratrol 3-O-glucuronide sebesar -8,1 kkal/mol dan prediksi Ki sebesar 1,137 MikroM. Berdasarkan studi penambatan molekuler dan prediksi drug-likeness, 6 senyawa polifenol yang berpotensi tersebut dapat dilanjutkan untuk penelitian lebih lanjut.
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