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Evaluation of dual potentiality of 2,4,5-trisubstituted oxazole derivatives as aquaporin-4 inhibitors and anti-inflammatory agents in lung cells

Inflammation is a multifaceted “second-line” adaptive defense mechanism triggered by exo/endogenous threating stimuli and inter-communicated by various inflammatory key players. Unresolved or dysregulated inflammation in lungs results in manifestation of diseases and leads to irreparable damage. Aqu...

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Autores principales: Meenakshi, Maniarasu, Kannan, Arun, Jothimani, Muralidharan, Selvi, Thangavel, Karthikeyan, Muthusamy, Prahalathan, Chidambaram, Srinivasan, Kannupal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472800/
https://www.ncbi.nlm.nih.gov/pubmed/37664213
http://dx.doi.org/10.1039/d3ra03989g
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author Meenakshi, Maniarasu
Kannan, Arun
Jothimani, Muralidharan
Selvi, Thangavel
Karthikeyan, Muthusamy
Prahalathan, Chidambaram
Srinivasan, Kannupal
author_facet Meenakshi, Maniarasu
Kannan, Arun
Jothimani, Muralidharan
Selvi, Thangavel
Karthikeyan, Muthusamy
Prahalathan, Chidambaram
Srinivasan, Kannupal
author_sort Meenakshi, Maniarasu
collection PubMed
description Inflammation is a multifaceted “second-line” adaptive defense mechanism triggered by exo/endogenous threating stimuli and inter-communicated by various inflammatory key players. Unresolved or dysregulated inflammation in lungs results in manifestation of diseases and leads to irreparable damage. Aquaporins (AQPs) are a ubiquitously expressed superfamily of intrinsic transmembrane water channel proteins that modulate the fluid homeostasis. In addition to their conventional functions, AQPs have clinical relevance to inflammation prevailing under the infectious conditions of various lung diseases and this proclaims them as appropriate biomarkers to be targeted. Hence an endeavor was undertaken to identify potential ligands to target AQP4 for the treatment of lung diseases. Oxazole being a versatile bio-potent core, a series of 2,4,5-trisubstituted oxazoles 3a–j were synthesized by a Lewis acid mediated reaction of aroylmethylidene malonates with nitriles. In silico studies conducted using the protein data bank (PDB) structure 3gd8 for AQP4 revealed that compound 3a would serve as a suitable candidate to inhibit AQP4 in human lung cells (NCI-H460). Further, in vitro studies demonstrated that compound 3a could effectively inhibit AQP4 and inflammatory cytokines in lung cells and hence it may be considered as a viable drug candidate for the treatment of various lung diseases.
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spelling pubmed-104728002023-09-02 Evaluation of dual potentiality of 2,4,5-trisubstituted oxazole derivatives as aquaporin-4 inhibitors and anti-inflammatory agents in lung cells Meenakshi, Maniarasu Kannan, Arun Jothimani, Muralidharan Selvi, Thangavel Karthikeyan, Muthusamy Prahalathan, Chidambaram Srinivasan, Kannupal RSC Adv Chemistry Inflammation is a multifaceted “second-line” adaptive defense mechanism triggered by exo/endogenous threating stimuli and inter-communicated by various inflammatory key players. Unresolved or dysregulated inflammation in lungs results in manifestation of diseases and leads to irreparable damage. Aquaporins (AQPs) are a ubiquitously expressed superfamily of intrinsic transmembrane water channel proteins that modulate the fluid homeostasis. In addition to their conventional functions, AQPs have clinical relevance to inflammation prevailing under the infectious conditions of various lung diseases and this proclaims them as appropriate biomarkers to be targeted. Hence an endeavor was undertaken to identify potential ligands to target AQP4 for the treatment of lung diseases. Oxazole being a versatile bio-potent core, a series of 2,4,5-trisubstituted oxazoles 3a–j were synthesized by a Lewis acid mediated reaction of aroylmethylidene malonates with nitriles. In silico studies conducted using the protein data bank (PDB) structure 3gd8 for AQP4 revealed that compound 3a would serve as a suitable candidate to inhibit AQP4 in human lung cells (NCI-H460). Further, in vitro studies demonstrated that compound 3a could effectively inhibit AQP4 and inflammatory cytokines in lung cells and hence it may be considered as a viable drug candidate for the treatment of various lung diseases. The Royal Society of Chemistry 2023-09-01 /pmc/articles/PMC10472800/ /pubmed/37664213 http://dx.doi.org/10.1039/d3ra03989g Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Meenakshi, Maniarasu
Kannan, Arun
Jothimani, Muralidharan
Selvi, Thangavel
Karthikeyan, Muthusamy
Prahalathan, Chidambaram
Srinivasan, Kannupal
Evaluation of dual potentiality of 2,4,5-trisubstituted oxazole derivatives as aquaporin-4 inhibitors and anti-inflammatory agents in lung cells
title Evaluation of dual potentiality of 2,4,5-trisubstituted oxazole derivatives as aquaporin-4 inhibitors and anti-inflammatory agents in lung cells
title_full Evaluation of dual potentiality of 2,4,5-trisubstituted oxazole derivatives as aquaporin-4 inhibitors and anti-inflammatory agents in lung cells
title_fullStr Evaluation of dual potentiality of 2,4,5-trisubstituted oxazole derivatives as aquaporin-4 inhibitors and anti-inflammatory agents in lung cells
title_full_unstemmed Evaluation of dual potentiality of 2,4,5-trisubstituted oxazole derivatives as aquaporin-4 inhibitors and anti-inflammatory agents in lung cells
title_short Evaluation of dual potentiality of 2,4,5-trisubstituted oxazole derivatives as aquaporin-4 inhibitors and anti-inflammatory agents in lung cells
title_sort evaluation of dual potentiality of 2,4,5-trisubstituted oxazole derivatives as aquaporin-4 inhibitors and anti-inflammatory agents in lung cells
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472800/
https://www.ncbi.nlm.nih.gov/pubmed/37664213
http://dx.doi.org/10.1039/d3ra03989g
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