A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic

Abstract Following our recent discovery of a new scaffold exhibiting significant neurotrophic and neurogenic activities, a structurally tweaked analogue, embodying a 2-oxa-spiro [5.4]decane framework, has been conceptualised and found to be more potent and versatile. It exhibits enhanced neurotrophi...

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Autores principales:	Pranav Chintamani Joshi, Ramesh Samineni, Dwaipayan Bhattacharya, Bommana Raghunath Reddy, Lenin Veeraval, Tapatee Das, Swati Maitra, Abhipradnya Bipin Wahul, Shailaja Karri, Srihari Pabbaraja, Goverdhan Mehta, Arvind Kumar, Sumana Chakravarty
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b47189658eb4e4eb51a8e26cd13875c
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spelling	oai:doaj.org-article:3b47189658eb4e4eb51a8e26cd13875c2021-12-02T12:31:51ZA 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic10.1038/s41598-017-01297-z2045-2322https://doaj.org/article/3b47189658eb4e4eb51a8e26cd13875c2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01297-zhttps://doaj.org/toc/2045-2322Abstract Following our recent discovery of a new scaffold exhibiting significant neurotrophic and neurogenic activities, a structurally tweaked analogue, embodying a 2-oxa-spiro [5.4]decane framework, has been conceptualised and found to be more potent and versatile. It exhibits enhanced neurotrophic and neurogenic action in in vitro, ex vivo and in vivo models and also shows robust neuroprotection in mouse acute cerebral stroke model. The observed attributes are traceable to the predominant activation of the TrkB-PI3K-AKT-CREB pathway. In addition, it also exhibits remarkable anti-neuroinflammatory activity by concurrently down-regulating pro-inflammatory cytokines IL-1α and IL-6, thereby providing a unique molecule with a trinity of neuroactivities, i.e. neurotrophic, neurogenic and anti-inflammatory. The new chemical entity disclosed here has the potential to be advanced as a versatile therapeutic molecule to treat stroke, depression, and possibly other neuropsychiatric disorders associated with attenuated neurotrophic/ neurogenic activity, together with heightened neuroinflammation.Pranav Chintamani JoshiRamesh SamineniDwaipayan BhattacharyaBommana Raghunath ReddyLenin VeeravalTapatee DasSwati MaitraAbhipradnya Bipin WahulShailaja KarriSrihari PabbarajaGoverdhan MehtaArvind KumarSumana ChakravartyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pranav Chintamani Joshi Ramesh Samineni Dwaipayan Bhattacharya Bommana Raghunath Reddy Lenin Veeraval Tapatee Das Swati Maitra Abhipradnya Bipin Wahul Shailaja Karri Srihari Pabbaraja Goverdhan Mehta Arvind Kumar Sumana Chakravarty A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic
description	Abstract Following our recent discovery of a new scaffold exhibiting significant neurotrophic and neurogenic activities, a structurally tweaked analogue, embodying a 2-oxa-spiro [5.4]decane framework, has been conceptualised and found to be more potent and versatile. It exhibits enhanced neurotrophic and neurogenic action in in vitro, ex vivo and in vivo models and also shows robust neuroprotection in mouse acute cerebral stroke model. The observed attributes are traceable to the predominant activation of the TrkB-PI3K-AKT-CREB pathway. In addition, it also exhibits remarkable anti-neuroinflammatory activity by concurrently down-regulating pro-inflammatory cytokines IL-1α and IL-6, thereby providing a unique molecule with a trinity of neuroactivities, i.e. neurotrophic, neurogenic and anti-inflammatory. The new chemical entity disclosed here has the potential to be advanced as a versatile therapeutic molecule to treat stroke, depression, and possibly other neuropsychiatric disorders associated with attenuated neurotrophic/ neurogenic activity, together with heightened neuroinflammation.
format	article
author	Pranav Chintamani Joshi Ramesh Samineni Dwaipayan Bhattacharya Bommana Raghunath Reddy Lenin Veeraval Tapatee Das Swati Maitra Abhipradnya Bipin Wahul Shailaja Karri Srihari Pabbaraja Goverdhan Mehta Arvind Kumar Sumana Chakravarty
author_facet	Pranav Chintamani Joshi Ramesh Samineni Dwaipayan Bhattacharya Bommana Raghunath Reddy Lenin Veeraval Tapatee Das Swati Maitra Abhipradnya Bipin Wahul Shailaja Karri Srihari Pabbaraja Goverdhan Mehta Arvind Kumar Sumana Chakravarty
author_sort	Pranav Chintamani Joshi
title	A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic
title_short	A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic
title_full	A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic
title_fullStr	A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic
title_full_unstemmed	A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic
title_sort	2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile cns therapeutic
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3b47189658eb4e4eb51a8e26cd13875c
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A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic

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