TY - JOUR
T1 - Integrated computational approach toward discovery of multi-targeted natural products from Thumbai (Leucas aspera) for attuning NKT cells
AU - Baruah, Vishwa Jyoti
AU - Paul, Rasana
AU - Gogoi, Dhrubajyoti
AU - Mazumder, Nirmal
AU - Chakraborty, Subrata
AU - Das, Aparoopa
AU - Mondal, Tapan Kumar
AU - Sarmah, Bhaswati
N1 - Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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. Communicated by Ramaswamy H. Sarma.
AB - 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. Communicated by Ramaswamy H. Sarma.
UR - http://www.scopus.com/inward/record.url?scp=85096133462&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096133462&partnerID=8YFLogxK
U2 - 10.1080/07391102.2020.1844056
DO - 10.1080/07391102.2020.1844056
M3 - Article
C2 - 33179569
AN - SCOPUS:85096133462
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
SN - 0739-1102
ER -