Author(s): Mokhamad Fahmi Rizki Syaban, Rislan Faiz Muhammad, Basyar Adnani, Gumilar Fardhani Ami Putra, Nabila Erina Erwan, Safira Dita Arviana, Agung Dwi Krisnayana, Dedy Budi Kurniawan

Email(s): mokhamadfahmi@gmail.com

DOI: 10.52711/0974-360X.2022.00513   

Address: Mokhamad Fahmi Rizki Syaban1*, Rislan Faiz Muhammad2, Basyar Adnani2, Gumilar Fardhani Ami Putra2, Nabila Erina Erwan2, Safira Dita Arviana2, Agung Dwi Krisnayana1, Dedy Budi Kurniawan2
1Faculty of Medicine, Brawijaya Univesity, Malang, 65111 Indonesia.
2Master Program in Biomedical Science, Faculty of Medicine, Brawijaya Univesity, Malang, 65111, Indonesia.
*Corresponding Author

Published In:   Volume - 15,      Issue - 7,     Year - 2022


ABSTRACT:
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)-3ß 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-3ß 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-3ß 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


Cite this article:
Mokhamad Fahmi Rizki Syaban, Rislan Faiz Muhammad, Basyar Adnani, Gumilar Fardhani Ami Putra, Nabila Erina Erwan, Safira Dita Arviana, Agung Dwi Krisnayana, Dedy Budi Kurniawan. 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. Research Journal of Pharmacy and Technology. 2022; 15(7):3069-4. doi: 10.52711/0974-360X.2022.00513

Cite(Electronic):
Mokhamad Fahmi Rizki Syaban, Rislan Faiz Muhammad, Basyar Adnani, Gumilar Fardhani Ami Putra, Nabila Erina Erwan, Safira Dita Arviana, Agung Dwi Krisnayana, Dedy Budi Kurniawan. 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. Research Journal of Pharmacy and Technology. 2022; 15(7):3069-4. doi: 10.52711/0974-360X.2022.00513   Available on: https://rjptonline.org/AbstractView.aspx?PID=2022-15-7-35


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