In Silico Prediction of Quercetin Analogs for Targeting Death-Associated Protein Kinase 1 (DAPK1) Against Alzheimer’s Disease

Title:In Silico Prediction of Quercetin Analogs for Targeting Death-Associated Protein Kinase 1 (DAPK1) Against Alzheimer’s Disease

Volume: 22 Issue: 14

Author(s): Yilu Sun, Jia Zhao, Yizhu Lu, Fung Yin Ngo, Bo Shuai, Zhang-Jin Zhang, Yibin Feng*Jianhui Rong*

Affiliation:

• School of Chinese Medicine, The University of Hong Kong, 3 Sassoon Road, Pokfulam, Hong Kong, China

• School of Chinese Medicine, The University of Hong Kong, 3 Sassoon Road, Pokfulam, Hong Kong, China

Abstract: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that greatly affects the health and life quality of the elderly population. Existing drugs mainly alleviate symptoms but fail to halt disease progression, underscoring the urgent need for the development of novel drugs. Based on the neuroprotective effects of flavonoid quercetin in AD, this study was designed to identify potential AD-related targets for quercetin and perform in silico prediction of promising analogs for the treatment of AD. Database mining suggested death-associated protein kinase 1 (DAPK1) as the most promising AD-related target for quercetin among seven protein candidates. To achieve better biological effects for the treatment of AD, we devised a series of quercetin analogs as ligands for DAPK1, and molecular docking analyses, absorption, distribution, metabolism, and excretion (ADME) predictions, as well as molecular dynamics (MD) simulations, were performed. The energy for drug-protein interaction was predicted and ranked. As a result, quercetin-A1a and quercetin-A1a1 out of 19 quercetin analogs exhibited the lowest interaction energy for binding to DAPK1 than quercetin, and they had similar dynamics performance with quercetin. In addition, quercetin-A1a and quercetin-A1a1 were predicted to have better water solubility. Thus, quercetin-A1a and quercetin-A1a1 could be promising agents for the treatment of AD. Our findings paved the way for further experimental studies and the development of novel drugs.

Cite this article as:

Sun Yilu, Zhao Jia, Lu Yizhu, Ngo Yin Fung, Shuai Bo, Zhang Zhang-Jin, Feng Yibin*, Rong Jianhui*, In Silico Prediction of Quercetin Analogs for Targeting Death-Associated Protein Kinase 1 (DAPK1) Against Alzheimer’s Disease, Current Neuropharmacology 2024; 22 (14) . https://dx.doi.org/10.2174/1570159X22666240515090434