ALMIRA PINKAN CARISSA, - (2026) SIMULASI DINAMIKA MOLEKULER ANDROGRAFOLID DAN 2 TURUNANNYA TERHADAP ACETYLCHOLINESTERASE DAN BETA-SECRETASE 1 SEBAGAI KANDIDAT ANTI ALZHEIMER. Skripsi thesis, Sekolah Tinggi Farmasi Indonesia.
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Abstract
Penyakit Alzheimer merupakan penyakit neurodegeneratif progresif yang ditandai oleh penurunan fungsi kognitif dan memori, dengan acetylcholinesterase (AChE) dan β-secretase 1 (BACE1) sebagai dua target terapeutik utama. Penelitian ini bertujuan mengevaluasi potensi andrografolid, asam andrografik, dan 14-deoksi11,12-didehidroandrografolid sebagai kandidat inhibitor multitarget AChE dan BACE1 melalui simulasi dinamika molekuler selama 10 ns, dengan donepezil dan verubecestat sebagai kontrol positif serta E20 dan M7D sebagai ligan alami. Parameter yang dianalisis meliputi Root Mean Square Deviation, Root Mean Square Fluctuation, okupansi ikatan hidrogen, dan energi bebas ikatan dengan metode MM-GBSA. Hasil simulasi menunjukkan bahwa seluruh kompleks uji mampu mempertahankan kestabilan konformasi, dengan 14-deoksi-11,12- didehidroandrografolid menunjukkan profil RMSD ligan paling stabil terhadap kedua reseptor, sementara fluktuasi residu terutama terjadi pada daerah loop dan terminal yang secara alami bersifat fleksibel. Analisis ikatan hidrogen menunjukkan interaksi persisten dengan residu-residu kunci pada sisi aktif kedua enzim. Berdasarkan perhitungan MM-GBSA, 14-deoksi-11,12- didehidroandrografolid menunjukkan afinitas pengikatan paling kompetitif terhadap AChE dengan nilai energi bebas total sebesar -42,9 kkal/mol, sedangkan andrografolid menunjukkan afinitas terbaik terhadap BACE1 dengan nilai -34,7 kkal/mol, mendekati ligan alami M7D. Secara keseluruhan, andrografolid dan turunannya berpotensi dikembangkan sebagai kandidat inhibitor multitarget AChE dan BACE1 untuk pengembangan agen terapeutik Alzheimer, meskipun validasi in vitro dan in vivo tetap diperlukan. ------ Alzheimer’s disease is a progressive neurodegenerative disease characterized by a decline in cognitive and memory functions, with acetylcholinesterase (AChE) and β-secretase 1 (BACE1) as two major therapeutic targets. This study aimed to evaluate the potential of andrographolide, andrographic acid, and 14-deoxy-11,12- didehydroandrographolide as multitarget inhibitors of AChE and BACE1 through 10 ns molecular dynamics simulations, with donepezil and verubecestat as positive controls and E20 and M7D as native ligands. The analyzed parameters included root mean square deviation, root mean square fluctuation, hydrogen bond occupancy, and binding free energy calculated using the MM-GBSA method. The simulation results showed that all test complexes were able to maintain conformational stability, with 14-deoxy-11,12-didehydroandrographolide exhibiting the most stable ligand RMSD profile toward both receptors, while residue fluctuations mainly occurred in loop and terminal regions that are naturally flexible. Hydrogen bond analysis revealed persistent interactions with key residues in the active sites of both enzymes. Based on the MM-GBSA calculations, 14-deoxy11,12-didehydroandrographolide showed the most competitive binding affinity toward AChE, with a total free energy value of −42.9 kcal/mol, whereas andrographolide showed the best affinity toward BACE1, with a value of −34.7 kcal/mol, approaching that of the native ligand M7D. Overall, andrographolide and its derivatives have the potential to be developed as multitarget inhibitors of AChE and BACE1 for the development of therapeutic agents for Alzheimer’s disease, although in vitro and in vivo validation is still required.
| Item Type: | Thesis (Skripsi) |
|---|---|
| Uncontrolled Keywords: | Alzheimer, andrografolid, AChE, BACE1, molecular docking, dinamika molekuler, MM-GBSA. ------- Alzheimer's disease, andrographolide, AChE, BACE1, molecular docking, molecular dynamics, MM-GBSA. |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Program Studi S1 Farmasi |
| Depositing User: | pustakawan - - |
| Date Deposited: | 23 Sep 2026 02:06 |
| Last Modified: | 23 Sep 2026 02:06 |
| URI: | http://repository.stfi.ac.id/id/eprint/4268 |
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