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• W1566657518 endingPage "1821" @default.
• W1566657518 startingPage "1807" @default.
• W1566657518 abstract "Background and Purpose Neurodegenerative diseases are a major problem afflicting ageing populations; however, there are no effective treatments to stop their progression. Oxidative stress and neuroinflammation are common factors in their pathogenesis. Nuclear factor (erythroid‐derived 2)‐like 2 ( N rf2) is the master regulator of oxidative stress, and melatonin is an endogenous hormone with antioxidative properties that reduces its levels with ageing. We have designed a new compound that combines the effects of melatonin with N rf2 induction properties, with the idea of achieving improved neuroprotective properties. Experimental Approach Compound ITH 12674 is a hybrid of melatonin and sulforaphane designed to exert a dual drug–prodrug mechanism of action. We obtained the proposed hybrid in a single step. To test its neuroprotective properties, we used different in vitro models of oxidative stress related to neurodegenerative diseases and brain ischaemia. Key Results ITH 12674 showed an improved neuroprotective profile compared to that of melatonin and sulforaphane. ITH 12674 (i) mediated a concentration‐dependent protective effect in cortical neurons subjected to oxidative stress; (ii) decreased reactive oxygen species production; (iii) augmented GSH concentrations in cortical neurons; (iv) enhanced the N rf2–antioxidant response element transcriptional response in transfected HEK 293 T cells; and (v) protected organotypic cultures of hippocampal slices subjected to oxygen and glucose deprivation and re‐oxygenation from stress by increasing the expression of haem oxygenase‐1 and reducing free radical production. Conclusion and Implications ITH 12674 combines the signalling pathways of the parent compounds to improve its neuroprotective properties. This opens a new line of research for such hybrid compounds to treat neurodegenerative diseases." @default.
• W1566657518 created "2016-06-24" @default.
• W1566657518 creator A5020095075 @default.
• W1566657518 creator A5025456226 @default.
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• W1566657518 date "2015-02-10" @default.
• W1566657518 modified "2023-10-14" @default.
• W1566657518 title "Melatonin-sulforaphane hybrid ITH12674 induces neuroprotection in oxidative stress conditions by a ‘drug-prodrug’ mechanism of action" @default.
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• W1566657518 doi "https://doi.org/10.1111/bph.13025" @default.
• W1566657518 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4376458" @default.
• W1566657518 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25425158" @default.
• W1566657518 hasPublicationYear "2015" @default.
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