HUBUNGAN KUANTITATIF STRUKTUR-AKTIVITAS (HKSA), STUDI INTERAKSI, DAN PREDIKSI TOKSISITAS TURUNAN N1-ARILSULFONILTRIPTAMIN SEBAGAI ANTAGONIS RESEPTOR 5-HT6 UNTUK PENGOBATAN PENYAKIT ALZHEIMER
Alzheimer is a neurodegenerative disease that causes the interference with the structure and function of the brain. The main therapy for Alzheimer's disease is centered on decreasing levels of acetylcholine. However, there are still many symptoms of a decline in other cognitive functions that...
Saved in:
| Main Author: | |
|---|---|
| Format: | Final Project |
| Language: | Indonesia |
| Online Access: | https://digilib.itb.ac.id/gdl/view/40464 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | Alzheimer is a neurodegenerative disease that causes the interference with the structure and
function of the brain. The main therapy for Alzheimer's disease is centered on decreasing levels of
acetylcholine. However, there are still many symptoms of a decline in other cognitive functions that
cannot be overcome by this method of therapy. Therefore, a search for new compounds that can
modulate other G-protein-coupled receptors (GCPR) that have a better effect is done, which is 5-
HT6 receptor antagonists. This study was aimed to obtain the best Quantitative Structure and
Activity Relationship (QSAR) equations and new compounds with better antagonistic activity and
affinity for the 5-HT6 receptor, interaction study, and toxicity prediction. QSAR equation were done
by using GaussView 6.0, Gaussian 09, MOE 2014.09, and SPSS Statistics 25.0. Five descriptors were
used, including AM1_Eele, AM1_LUMO, ASA_H, log P, and log S. Compounds and receptor
ð??±? ®?ð???±?± ? ???±¸ ?!????????®ÿ ????????????????????????í± ®??????¸????????ð®ð???±?± ??±¸ð®?±¸ ???ð?ã
ADMET Predictor 7.1. The best QSAR equation which was validated by using the Leave One Out
(LOO) method and Fisher statistical analysis is Log C (µM) = -3,653 (± 1,711) + 1,563 * 10
-5
*
AM1_Eele + 1,454 (± 0.564) * AM1_LUMO + 0,022 (± 0.005) * ASA_H - 1,307 (± 0,285) * log P - 2,076
(± 0,364) * log S. The result of protein validation is the RMSD value of 0.969. Modified compound
number 30 is the best derivative compound with IC50 value of 0,5692 and binding energy of -9,71
kcal / mol. Modified compound number 30 has a better toxicity prediction than modified compound
number 8, and has an almost similar toxicity prediction with its parent compound.
|
|---|