PENDEKATAN MOLECULAR DOCKING PREDIKSI ADME DAN TOKSISITAS SENYAWA AKTIF BUAH PARE (Momordica charantia L.) SEBAGAI INHIBITOR α-AMYLASE

Yosua Christabel Natanael, Tiara Ajeng Listyani, Rahmat Hidayat

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Latar Belakang: Diabetes mellitus tipe 2 menjadi masalah kesehatan global dengan prevalensi tinggi di Indonesia, mencapai 10,9% pada 2023, didorong oleh resistensi insulin dan gangguan metabolisme karbohidrat. Obat sintetis seperti acarbose sering menimbulkan efek samping gastrointestinal, sehingga diperlukan alternatif alami dari pare yang kaya flavonoid seperti quercetin dan rutin. Tujuan: Penelitian bertujuan menganalisis interaksi 23 senyawa flavonoid pare dengan α-amylase melalui docking molecular, memprediksi profil ADME dan toksisitas, serta mendesain senyawa baru potensial sebagai kandidat antidiabetes.

Metode: Penelitian ini dilakukan secara in silico menggunakan PyRx-AutoDock Vina untuk docking, VegaZZ, PyMOL, dan Discovery Studio untuk optimasi dan visualisasi, SwissADME untuk ADME, Toxtree untuk toksisitas. Validasi metode docking dilakukan dengan RMSD <2 Å. Hasil: Hasil docking menunjukkan genistein memiliki binding affinity -7,4 kkal/mol, nilai RMSD 1,538 Å  dan genistein memiliki kemiripan dengan ligan natif pada residu ASP300. Genistein memiliki profil ADME yang baik, dan toksisitas yang buruk yaitu High Class III . Desain senyawa baru dari genistein yaitu 4-2-hydroxy-1-hydroxymethoxybutylcyclohexan-1-ol memiliki interaksi asam amino yang sama dengan liganatif dan kontrol positif yaitu ASP300, binding affinity -5,6 kkal/mol, nilai RMSD 1.223 Å, ADME yang baik, dan toksisitas yang rendah. Kesimpulan: Senyawa aktif buah pare berpotensi sebagai inhibitor α-amylase.

Kata kunci: α-Amylase, ADME, Molecular docking, Pare, Toksisitas


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Referensi


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DOI: https://doi.org/10.33024/jaf.v11i1.25053

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