Biochemical and behavioral characterization of IN14, a new inhibitor of HDACs with antidepressant-like properties

Heidy Martínez-pacheco, Ofir Picazo, Adolfo López-torres, Jean Pascal Morin, Karla Viridiana Castro-cerritos, Rossana Citlali Zepeda, Gabriel Roldán-roldán

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    Abstract

    Evidence suggests that histone deacetylases (HDACs) inhibitors could be used as an effective treatment for some psychiatric and neurological conditions such as depression, anxiety and age-related cognitive decline. However, non-specific HDAC inhibiting compounds have a clear disadvantage regarding their efficacy and safety, thus the need to develop more selective ones. The present study evaluated the toxicity, the capacity to inhibit HDAC activity and antidepressant-like activity of three recently described class I HDAC inhibitors IN01, IN04 and IN14, using A. salina toxicity test, in vitro fluorometric HDAC activity assay and forced-swimming test, respectively. Our data show that IN14 possesses a better profile than the other two. Therefore, the pro-cognitive and antidepressant effects of IN14 were evaluated. In the forced-swimming test model of depression, intraperitoneal administration of IN14 (100 mg/Kg/day) for five days decreased immobility, a putative marker of behavioral despair, significantly more than tricyclic antidepressant desipramine, while also increasing climbing behavior, a putative marker of motivational behavior. On the other hand, IN14 left the retention latency in the elevated T-maze unaltered. These results suggest that novel HDAC class I inhibitor IN14 may represent a promising new antidepressant with low toxicity and encourages further studies on this compound.

    Original languageEnglish
    Article number299
    JournalBiomolecules
    Volume10
    Issue number2
    DOIs
    StatePublished - Feb 2020

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    Keywords

    • Antidepressants
    • Chromatin remodeling
    • Class I HDAC
    • Drug design
    • Elevated T maze
    • Epigenetics
    • Forced-swimming test
    • Toxicity

    Cite this

    Martínez-pacheco, H., Picazo, O., López-torres, A., Morin, J. P., Castro-cerritos, K. V., Zepeda, R. C., & Roldán-roldán, G. (2020). Biochemical and behavioral characterization of IN14, a new inhibitor of HDACs with antidepressant-like properties. Biomolecules, 10(2), [299]. https://doi.org/10.3390/biom10020299