Penambatan Molekuler Senyawa Aktif Sirih Merah (Piper crocatum) pada Butirilkolinesterase sebagai Kandidat Antialzheimer

Rahmadi Ganesha Putri, Mega Safithri, Husnawati Husnawati, Rini Kurniasih

Abstract

Alzheimer adalah salah satu penyakit neurodegeneratif kronis dan menjadi penyakit yang sering dialami oleh orang lanjut usia. Perubahan yang terjadi dari penyakit Alzheimer, yakni penurunan fungsi kognitif, memori, dan perubahan perilaku secara permanen. Senyawa aktif pada daun sirih merah memiliki kesamaan kandungan dengan daun sirih hijau untuk menghambat butirilkolinesterase (BChE). Butirilkolinesterase adalah salah satu enzim yang berperan dalam penanganan penyakit Alzheimer dikaitkan dengan terbentuknya Alzheimer, yakni hipotesis kolinergik. Penelitian dilakukan menguji daya inhibisi senyawa aktif yang terkandung dalam daun sirih merah terhadap aktivitas butirilkolinesterase melalui pendekatan simulasi penambatan molekuler. Penelitian menggunakan dua metode, yakni penggabungan penapisan virtual dan penambatan molekuler sebagai tahapan awal pengembangan daun sirih merah terhadap aktivitas penghambatan butirilkolinesterase. Hasil dalam penelitian diperoleh, daya inhibisi terbaik ditemukan pada 1,2,3,4,5,6,7-heptazacycloicosane sebesar 0,4888 µM dan energi bebas pengikatan sebesar -8,6 kkal∙mol-1. Residu yang berperan dalam menghambat butirilkolinesterase, yakni pada pengikatan substrat oleh ligan uji, yakni Tyr-332 dan Trp-82. Hasil penelitian ini dapat dijadikan sebagai sumber referensi dalam menemukan alternatif pengobatan penyakit Alzheimer. 

Molecular Docking of the Active Compound of Red Betel (Piper crocatum) on Butyrylcholinesterase as an Antialzheimer's Candidate. Alzheimer's is a chronic neurodegenerative disease often experienced by the elderly. Changes that occur from Alzheimer's disease such as permanent decline in cognitive function, memory, and behavioral changes. The active compounds in red betel leaves have similar contents with green betel leaves to inhibit butyrylcholinesterase (BChE). Butyrylcholinesterase is an enzyme that may play an important role in the treatment of Alzheimer's disease associated with the formation of Alzheimer's, the cholinergic hypothesis. The study tested the inhibition power of the active compounds contained in red betel leaves against the activity of butyrylcholinesterase through a molecular docking simulation approach. The method in the study used the merger of virtual screening and molecular docking as the initial stage for the development of red betel leaves against the inhibitory activity of butyrylcholinesterase. The result in the study found the best inhibitiron power was found at 1,2,3,4,5,6,7-heptazacycloicosane of 0.4888 µM and binding free energy of -8.6 kkal∙mol-1. The residues that play a role in the inhibition of butyrylcholinesterase on substrate binding by test ligands were Tyr-332 and Trp-82. The research result can be used as a reference in finding alternative treatments for Alzheimer's disease. 

Keywords

antialzheimer; butyrylcholinesterase; molecular docking; Piper crocatum.

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DOI: https://doi.org/10.20961/alchemy.19.1.59676.68-85

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