Prediksi Inhibisi Lipase Pankreas oleh Senyawa Aktif Ekstrak Biji Kopi Robusta Leuwiliang Melalui Pendekatan In Silico

Abstract

Obesitas merupakan masalah kesehatan global yang memerlukan penemuan agen antiobesitas baru. Inhibisi lipase pankreas menjadi strategi efektif dalam mengurangi absorpsi lemak. Penelitian ini bertujuan mengidentifikasi senyawa aktif biji kopi Leuwiliang dan menganalisis potensi inhibisinya terhadap lipase pankreas secara in silico. Senyawa hasil profiling UPLC-QTOF-MS yang dilakukan oleh Karlina et al. (2025), diskrining menggunakan aturan Lipinski dan ADMET, kemudian dilakukan molecular docking terhadap enzim 1LPB dengan YASARA. Lima senyawa dengan binding energy tertinggi adalah cytochalasin B, 3,4-dikaefeoil-1,5-kuinolakton, 4-p-koumaroilkuinat, (2S)-2-Ammonio-4-{4-[(1Z)-2-({(3S)-1-[(R)-carboxylato(4-hydroxyphenyl)methyl]-2-oxo-3-azetidinyl} amino)-N-hydroxy-2-oxoethanimidoyl]phenoxy}butanoatato(8-), dan asam klorogenat. Seluruh senyawa berinteraksi dengan residu katalitik Ser152 dan/atau His263. Cytochalasin B memiliki afinitas tertinggi namun toksisitasnya kurang baik. Sebaliknya, asam klorogenat, 4-p-koumaroilkuinat, dan 3,4-dikaefeoil-1,5-kuinolakton menunjukkan kombinasi afinitas tinggi dan profil ADMET baik dengan absorpsi rendah yang ideal untuk target lokal di usus.

Obesity is a global health problem that requires the discovery of new anti-obesity agents. Inhibition of pancreatic lipase is an effective strategy to reduce fat absorption. This study aims to identify bioactive compounds in Leuwiliang coffee beans and analyze their inhibitory potential against pancreatic lipase through an in silico approach. Compounds obtained from UPLC-QTOF-MS profiling conducted by Karlina et al. (2025) were screened using Lipinski's rule and ADMET properties, followed by molecular docking against the 1LPB enzyme using YASARA. The five compounds with the highest binding energy were cytochalasin B, 3,4-dicaffeoyl-1,5-quinolactone, 4-p-coumaroylquinate, (2S)-2-ammonio-4-{4-[(1Z)-2-({(3S)-1-[(R)-carboxylato(4-hydroxyphenyl)methyl]-2-oxo-3-azetidinyl}amino)-N-hydroxy-2-oxoethanimidoyl]phenoxy}butanoate(8-), and chlorogenic acid. All compounds interacted with the catalytic residues Ser152 and/or His263. Cytochalasin B exhibited the highest affinity but had poor toxicity. In contrast, chlorogenic acid, 4-p-coumaroylquinate, and 3,4-dicaffeoyl-1,5-quinolactone showed a combination of high affinity and favorable ADMET profiles with low absorption, which is ideal for local targeting in the intestine.