ABSTRACT).

Alzheimer’s is a progressive and neurodegenerative disease that mainly affects people aged 65 years and older. The pathophysiology of Alzheimer’s is possibly related to the depletion of the neurotransmitter acetylcholine (ACh) due to beta-amyloid plaques and neurofibrillary tangles. Secondary metabolites found in cinnamon bark (Cinnamomum burmannii) have the potential as anticholinesterases to treat Alzheimer’s symptoms. This study aimed to identify the potency of bioactive compounds from cinnamon bark as AChE inhibitors in silico through analysis of binding energy, inhibition constants, and types of interactions. The research was conducted by screening virtually 60 test ligands using the PyRx program and molecular docking using the Autodock Tools program. The results of the ligand-receptor interaction analysis showed that 12 of the 15 tested ligands had potential as AChE inhibitors. Epicatechin and medioresinol are the ligands with the best potential for AChE inhibition with affinity close to the natural ligand or donepezil. Epicatechin has a binding energy of −10.0 kcal/mol and inhibition constant of 0.0459 M, with four hydrogen bonds and seven hydrophobic bonds. Meanwhile, medioresinol has −9.9 kcal/mol binding energy and inhibition constant of 0.0543 M, with one hydrogen bond and thirteen hydrophobic bonds.

This study aims to determine the inhibition of natural compounds P. crocatum against AChE enzyme activity. Inhibition of natural compounds of P. crocatum was analyzed by combining virtual screening and molecular docking methods with two different software, namely Autodock Tools 1.5.6 and YASARA Structure. This method is expected to improve the ability to identify potential natural compounds contained in betel leaf as AD drug candidates with AChE inhibition mechanism. A total of 21 natural compounds from three red betel leaf extract fractions (water fraction, ethyl acetate, and n-hexane) were analyzed for their binding affinity energy to AChE by virtual screening along with 664 active compounds known to have AChE inhibitory activity based on the DUD-E database to identify the potential of natural compounds for each fraction of red betel leaf (P. crocatum) inhibits AChE activity

Lisinopril (Angiotensin Converting Enzyme inhibitor) merupakan obat pilihan lini pertama dalam pengobatan hipertensi, namun obat tersebut masih memiliki banyak efek samping. Sirih merah telah banyak digunakan dalam pengobatan herbal dan diharapkan berpotensi menghambat aktivitas ACE (Angiotensin Converting Enzyme). Penelitian ini bertujuan untuk menemukan senyawa aktif yang berpotensi menghambat ACE in silico dengan metode molecular anchoring. Enzim ACE memiliki sisi pengikatan Metal binding yang mengikat di logam zinc, interaksi tersebut melibatkan asam amino HIS383, HIS387, dan GLU411. Situs aktif dari enzim ACE terletak pada asam amino GLU384. Ion zinc merupakan komponen penting dari ACE karena terikat pada situs aktif. Terdapat 7 ligan yang berinteraksi dengan asam amino penting sesuai ligan alami dan bernilai (bebas Gibbs dan Ki) lebih negatif dari ligan alaminya. Terdapat 1 ligan yang menjadi terbaik diantara 7 ligan yaitu, 3S,5R,8R,9R,10R,12R,13R,14R,17S)-17-[(2S)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-hydroxypentan-2-yl]- 4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,12- diol.

<p>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 <em>1,2,3,4,5,6,7-heptazacycloicosane</em> 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. </p><p><strong>Molecular Docking of the Active Compound of Red Betel (<em>Piper crocatum</em>) on Butyrylcholinesterase as an Antialzheimer's Candidate. </strong>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. </p>