TY - JOUR
T1 - Molecular Docking Studies of Interaction Curcumin against Beta-secretase 1, Amyloid A4 Protein, Gamma-secretase and Glycogen Synthase Kinase-3β as Target Therapy for Alzheimer Disease
AU - Syaban, Mokhamad Fahmi Rizki
AU - Muhammad, Rislan Faiz
AU - Adnani, Basyar
AU - Putra, Gumilar Fardhani Ami
AU - Erwan, Nabila Erina
AU - Arviana, Safira Dita
AU - Krisnayana, Agung Dwi
AU - Kurniawan, Dedy Budi
N1 - Publisher Copyright:
© RJPT All right reserved.
PY - 2022/7
Y1 - 2022/7
N2 - Alzheimer's disease (AD) is the most common form of dementia. In several studies we reviewed, curcumin can inhibit formation, extension, and destabilization of Amyloid A4 protein. Aim: This study aims to prove the consistency of curcumin as a candidate therapy for Alzheimer's disease using in silico approach. Methods: Biomolecular experimental study was conducted using in silico method supported by protein database, Pymol, Discovery studio, and PyRx software. A comprehensive literature search was conducted to found the potential target for Alzheimer's disease. We found Beta-secretase 1, Amyloid A4 protein, Gamma-secretase, and Glycogen synthase kinase (GSK)-3β as a protein target. Pharmacokinetic analysis was conducted based on the Lipinski Rule of Five criteria on the Lipinski Rule of Five websites and using the PreADMET website. Results: From the pharmacokinetic analysis, curcumin had met all the Lipinski and PreADMET criteria. The HIA and plasma binding test results showed 94.4% and 88%, which represent a good pharmacokinetic and bioavailability profile as a drug. GSK-3β had the strongest binding affinity with curcumin as recorded as-8.3 kcal/mol compared with the other four protein targets in this analysis. Conclusion: The strongest binding affinity between curcumin and GSK-3β reveals the potential target protein for Alzheimer's Disease therapy. Those interactions represent the potential involvement in the pathogenesis of Alzheimer's Disease with a modification of the additional sites on the tau molecule. This drug candidate discovery shows a preferable pharmacokinetics and bioavailability substance profile with a promising target through the Structure-based Drug Design (SBDD) approach. However, curcumin ability for BBB penetration still needs to be modified to improve its pharmacokinetic properties for becoming a novel Alzheimer's disease drug.
AB - Alzheimer's disease (AD) is the most common form of dementia. In several studies we reviewed, curcumin can inhibit formation, extension, and destabilization of Amyloid A4 protein. Aim: This study aims to prove the consistency of curcumin as a candidate therapy for Alzheimer's disease using in silico approach. Methods: Biomolecular experimental study was conducted using in silico method supported by protein database, Pymol, Discovery studio, and PyRx software. A comprehensive literature search was conducted to found the potential target for Alzheimer's disease. We found Beta-secretase 1, Amyloid A4 protein, Gamma-secretase, and Glycogen synthase kinase (GSK)-3β as a protein target. Pharmacokinetic analysis was conducted based on the Lipinski Rule of Five criteria on the Lipinski Rule of Five websites and using the PreADMET website. Results: From the pharmacokinetic analysis, curcumin had met all the Lipinski and PreADMET criteria. The HIA and plasma binding test results showed 94.4% and 88%, which represent a good pharmacokinetic and bioavailability profile as a drug. GSK-3β had the strongest binding affinity with curcumin as recorded as-8.3 kcal/mol compared with the other four protein targets in this analysis. Conclusion: The strongest binding affinity between curcumin and GSK-3β reveals the potential target protein for Alzheimer's Disease therapy. Those interactions represent the potential involvement in the pathogenesis of Alzheimer's Disease with a modification of the additional sites on the tau molecule. This drug candidate discovery shows a preferable pharmacokinetics and bioavailability substance profile with a promising target through the Structure-based Drug Design (SBDD) approach. However, curcumin ability for BBB penetration still needs to be modified to improve its pharmacokinetic properties for becoming a novel Alzheimer's disease drug.
KW - Alzheimer
KW - Amyloid A4 Protein
KW - Beta-secretase 1
KW - Curcumin
KW - Gamma-secretase
KW - Glycogen Synthase Kinase-3β
KW - Molecular Docking
UR - http://www.scopus.com/inward/record.url?scp=85137091419&partnerID=8YFLogxK
U2 - 10.52711/0974-360X.2022.00513
DO - 10.52711/0974-360X.2022.00513
M3 - Article
AN - SCOPUS:85137091419
SN - 0974-3618
VL - 15
SP - 3069
EP - 3074
JO - Research Journal of Pharmacy and Technology
JF - Research Journal of Pharmacy and Technology
IS - 7
ER -