In Silico Evaluation of Marine Phytochemicals as Potential Inhibitors of Inhibitor-Kappa B Protein Kinase (IκK) for Alzheimer’s Disease Therapeutics

Deepak Sheokand, Annu Grewal, Vivek Kumar, Raveena Chauhan, Vandana Saini and Ajit Kumar*

Toxicology and Computational Biology Group, Centre for Bioinformatics Maharshi Dayanand University, Rohtak, Haryana, India

Corresponding Author E-mail: akumar.cbt.mdu@gmail.com

DOI : http://dx.doi.org/10.13005/bbra/3286

ABSTRACT: Alzheimer's disease (AD) is a polygenic, progressive neurodegenerative condition that leads to cognitive and behavioural impairment. The drugs available for AD have been found vital for symptomatic cognitive treatment, but cannot treat or slow down the disease's progression, besides having severe side effects. Plants have been extensively used in traditional medicine, and marine phytochemicals have also been proven as a legitimate solution for several ailments. This study was carried out to screen marine phytochemicals for AD therapy and neuroinflammation by focusing on inhibiting the neuroinflammatory pathway involved in AD progression and nervous system degeneration using IκK as the therapeutic target protein. Virtual screening of 2583 marine phytochemicals retrieved from the Comprehensive Marine Natural Products Database (CMNPD) was performed for Lipinski's rule, ADME/T profiling, Blood-brain permeability and molecular docking studies using IκK as the target receptor and Curcumin as the standard inhibitor of IκK.  Seven marine phytochemicals (CMNPD IDs: CMNPD25050, CMNPD793, CMNPD18964, CMNPD14904, CMNPD31514, CMNPD24296) showed better binding affinity when docked against IκK as compared to the standard compound Curcumin and are the potential lead molecules to be further evaluated for AD therapy. Molecular dynamics simulations were also performed to investigate the binding interactions and stability of the top-hit marine phytochemical CMNPD25050 (8,11-dihydro-1-methoxy laurokamuren-12-ol) with the IκK target protein.

KEYWORDS: Marine natural products; Molecular modelling; Molecular docking; Nuclear factor-kappa B (NF- κB); Virtual Screening

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