TY - JOUR
T1 - Biochemical and behavioral characterization of IN14, a new inhibitor of HDACs with antidepressant-like properties
AU - Martínez-pacheco, Heidy
AU - Picazo, Ofir
AU - López-torres, Adolfo
AU - Morin, Jean Pascal
AU - Castro-cerritos, Karla Viridiana
AU - Zepeda, Rossana Citlali
AU - Roldán-roldán, Gabriel
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Antidepressants
KW - Chromatin remodeling
KW - Class I HDAC
KW - Drug design
KW - Elevated T maze
KW - Epigenetics
KW - Forced-swimming test
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=85079589862&partnerID=8YFLogxK
U2 - 10.3390/biom10020299
DO - 10.3390/biom10020299
M3 - Artículo
C2 - 32075023
AN - SCOPUS:85079589862
SN - 2218-273X
VL - 10
JO - Biomolecules
JF - Biomolecules
IS - 2
M1 - 299
ER -