PUBLICATION
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
- Authors
- Joshi, P.C., Samineni, R., Bhattacharya, D., Reddy, B.R., Veeraval, L., Das, T., Maitra, S., Wahul, A.B., Karri, S., Pabbaraja, S., Mehta, G., Kumar, A., Chakravarty, S.
- ID
- ZDB-PUB-181218-9
- Date
- 2017
- Source
- Scientific Reports 7: 1492 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Anti-Anxiety Agents/pharmacology
- Anti-Anxiety Agents/therapeutic use
- Antidepressive Agents/pharmacology
- Antidepressive Agents/therapeutic use
- Cell Death/drug effects
- Cell Differentiation/drug effects
- Central Nervous System/drug effects*
- Disease Models, Animal
- Inflammation/pathology*
- Ischemia/pathology
- Male
- Mice, Inbred C57BL
- Nerve Growth Factors/genetics
- Nerve Growth Factors/metabolism*
- Neurites/drug effects
- Neurites/metabolism
- Neurogenesis/drug effects*
- Neuroprotective Agents/pharmacology
- Neuroprotective Agents/therapeutic use
- Protein Kinase Inhibitors/pharmacology
- Spiro Compounds/chemistry
- Spiro Compounds/pharmacology*
- Spiro Compounds/therapeutic use*
- Transcription, Genetic/drug effects
- Zebrafish
- PubMed
- 28473714 Full text @ Sci. Rep.
Citation
Joshi, P.C., Samineni, R., Bhattacharya, D., Reddy, B.R., Veeraval, L., Das, T., Maitra, S., Wahul, A.B., Karri, S., Pabbaraja, S., Mehta, G., Kumar, A., Chakravarty, S. (2017) 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. Scientific Reports. 7:1492.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping