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Open AccessArticle

Biochemical and Behavioral Characterization of IN14, a New Inhibitor of HDACs with Antidepressant-Like Properties

1
Laboratorio de Neurobiología Conductual, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, México
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Sección de Estudios de Posgrado e Investigación de la Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340 México
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Instituto de Química Aplicada, Universidad del Papaloapan, Campus Tuxtepec, Circuito Central 200, Parque Industrial, Tuxtepec, Oaxaca 68301, México
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Centro de Investigaciones Biomédicas, Universidad Veracruzana. Av. Dr. Luis Castelazo Ayala s/n. Col., Industrial Ánimas, Xalapa, Veracruz 91190, México
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(2), 299; https://doi.org/10.3390/biom10020299
Received: 31 December 2019 / Revised: 6 February 2020 / Accepted: 12 February 2020 / Published: 14 February 2020
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.
Keywords: chromatin remodeling; antidepressants; toxicity; forced-swimming test; drug design; epigenetics; elevated T maze; class I HDAC chromatin remodeling; antidepressants; toxicity; forced-swimming test; drug design; epigenetics; elevated T maze; class I HDAC
MDPI and ACS Style

Martínez-Pacheco, H.; Picazo, O.; López-Torres, A.; Morin, J.-P.; Castro-Cerritos, K.V.; Zepeda, R.C.; Roldán-Roldán, G. Biochemical and Behavioral Characterization of IN14, a New Inhibitor of HDACs with Antidepressant-Like Properties. Biomolecules 2020, 10, 299.

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