Integrated computational approach toward discovery of multi-targeted naturalproducts from Thumbai (Leucas aspera) for attuning NKT cells

Mazumder, Nirmal (2022) Integrated computational approach toward discovery of multi-targeted naturalproducts from Thumbai (Leucas aspera) for attuning NKT cells. Journal of Biomolecular Structure and Dynamics, 40 (7). pp. 2893-2907. ISSN 0739-1102

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Abstract

A multi-omics-based approach targeting the plant-based natural products from Thumbai (Leucas aspera), an important yet untapped potential source of many therapeutic agents for myriads of immunological conditions and genetic disorders, was conceptualized to reconnoiter its potential biomedical application. A library of 79 compounds from this plant was created, out of which 9 compounds qualified the pharmacokinetics parameters. Reverse pharmacophore technique for target fishing of the screened compounds was executed through which renin receptor (ATP6AP2) and thymidylate kinase (DTYMK) were identified as potential targets. Network biology approaches were used to comprehend and validate the functional, biochemical and clinical relevance of the targets. The target–ligand interaction and subsequent stability parameters at molecular scale were investigated using multiple strategies including molecular modeling, pharmacophore approaches and molecular dynamics simulation. Herein, isololiolide and 4-hydroxy-2-methoxycinnamaldehyde were substantiated as the lead molecules exhibiting comparatively the best binding affinity against the two putative protein targets. These natural lead products from L. aspera and the combinatorial effects may have plausible medical applications in a wide variety of neurodegenerative, genetic and developmental disorders.The lead molecules also exhibit promising alternative in diagnostics and therapeutics through immuno-modulation targeting natural killer T-cell function in transplantation-related pathogenesis,autoimmune and other immunological disorders

Item Type: Article
Uncontrolled Keywords: Biomedical network; Leucas aspera; Molecular docking; Molecular dynamics simulation; NKT cells
Subjects: Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 09 May 2022 06:31
Last Modified: 09 May 2022 06:31
URI: http://eprints.manipal.edu/id/eprint/158671

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