Analisis In Silico Senyawa Aktif Jahe Merah (Zingiber officinale var. Rubrum) sebagai Inhibitor Asetilkolinesterase

Abstract

Pengobatan menggunakan inhibitor asetilkolinesterase (AChE) telah banyak dilakukan, namun obat tersebut masih memberikan banyak efek samping. Penelitian secara in vitro terkait jahe merah telah terbukti berpotensi sebagai inhibitor AChE, namun belum diketahui senyawa dan interaksinya secara in silico. Penelitian ini bertujuan mengidentifikasi senyawa aktif jahe merah yang berpotensi menginhibisi AChE serta analisis interaksi yang terjadi secara in silico. Senyawa aktif jahe merah dari literatur ditambatkan ke reseptor AChE, kemudian diprediksi bioavailabilitas dan toksisitas ligannya serta dianalisis interaksinya. Hasil penelitian menunjukkan galanthamine (ligan alami), donepezil, dan rivastigmine (ligan pembanding) memiliki nilai ∆G sebesar -10,5710, -10,3260, dan -7,3670 kkal/mol serta Ki sebesar 0,0175, 0,0265, dan 3,9261 µM, potensi inhibisi terbaik dimiliki oleh ligan fisetin dan morin dengan ∆G sebesar -10,4250 dan -10,3570 kkal/mol serta Ki sebesar 0,0224 dan 0,0251 µM. Kedua ligan memiliki nilai ∆G lebih negatif daripada ligan pembanding dan berikatan dengan situs aktif secara kuat pada residu asam amino HIS447, sehingga dapat berpotensi sebagai inhibitor kompetitif enzim AChE serta bersifat mudah larut dan tidak toksik bagi tubuh.

Treatment using acetylcholinesterase (AChE) inhibitors has been widely used, but these drugs still have many side effects. In vitro research related to red ginger has shown potential as an AChE inhibitor, but the compounds and their in silico interactions are unknown. This study aims to identify the active compounds in red ginger that have the potential to inhibit AChE and to analyze the interactions that occur in silico. The active compound of red ginger from the literature was tethered to the AChE receptor, then the bioavailability and toxicity of the ligands were predicted and their interactions were analyzed. The results showed that galanthamine (natural ligand), donepezil, and rivastigmine (comparison ligand) had ∆G values of -10.5710, -10.3260 and -7.3670 kcal/mol and Ki of 0.0175, 0.0265, and 3.9261 µM, the best inhibition potential is owned by fisetin and morin ligands with ∆G of -10.4250 and -10.3570 kcal/mol and Ki of 0.0224 and 0.0251 µM. Both ligands have more negative ∆G values than the comparison ligands and bind strongly to the active site on the HIS447 amino acid residue, so they can potentially act as competitive inhibitors of the AChE enzyme and are easily soluble and not toxic to the body.