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


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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.

About the authors

Yilu Sun

Department of Chinese Medicine, The University of Hong Kong Shenzhen Hospital

Email: info@benthamscience.net

Jia Zhao

Department of Chinese Medicine, The University of Hong Kong Shenzhen Hospital

Email: info@benthamscience.net

Yizhu Lu

School of Chinese Medicine, The University of Hong Kong

Email: info@benthamscience.net

Fung Ngo

School of Chinese Medicine, The University of Hong Kong

Email: info@benthamscience.net

Bo Shuai

Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Email: info@benthamscience.net

Zhang-Jin Zhang

Department of Chinese Medicine, The University of Hong Kong Shenzhen Hospital

Email: info@benthamscience.net

Yibin Feng

School of Chinese Medicine, The University of Hong Kong

Author for correspondence.
Email: info@benthamscience.net

Jianhui Rong

School of Chinese Medicine, The University of Hong Kong

Author for correspondence.
Email: info@benthamscience.net

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