Identification of Withanolide G as a Potential Inhibitor of Rho-associated
Kinase-2 Catalytic Domain to Confer Neuroprotection in Ischemic Stroke
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Published:2023-07
Issue:7
Volume:20
Page:845-853
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ISSN:1570-1808
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Container-title:Letters in Drug Design & Discovery
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language:en
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Short-container-title:LDDD
Author:
Kumar Gaurav1ORCID,
Sinha Ambarish Kumar1,
Dahiya Kajal1
Affiliation:
1. Department of Biosciences, School of Basic and Applied Sciences, Galgotias University, Greater Noida, Uttar Pradesh,
India
Abstract
Background:
Cerebral stroke is one of the leading causes of death and disability in a large
number of patients globally. Brain damage in ischemic stroke is led by a complex cascade of events. The
Rho-associated kinase-2 (ROCK2) has a significant role in cerebral vasospasm, vascular remodeling, and
inflammation. It is activated in cerebral ischemia and its inhibition leads to a neuroprotective effect.
Objective:
The present study is designed to identify potential inhibitors of ROCK2 using a molecular
docking approach.
Method:
We docked phytochemicals of Withania somnifera (WS) into the catalytic site of ROCK2 and
compared results with inhibitor Y-27632. ADME and drug-likeness properties of WS phytochemicals
were also analyzed.
Results:
Results suggest that 11 phytochemicals exhibited higher binding affinity toward the ROCK2
catalytic domain compared to the Y-27632 inhibitor. Among these phytochemicals, Withanolide G
formed H-bonding and established hydrophobic contacts with key catalytic domain residues of ROCK2.
Conclusion:
Our findings suggest that Withanolide G has the potential to inhibit the action of ROCK2
and can be developed as a neurotherapeutic agent to combat cerebral ischemic insult.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine