|
KMID : 1204320210370010027
|
|
Laboratory Animal Research
2021 Volume.37 No. 1 p.27 ~ p.27
|
|
|
Zebrafish toxicological screening could aid Leishmaniosis drug discovery
|
|
Fukushima Hirla Costa Silva
Bailone Ricardo Lacava
Correa Tatiana
Janke Helena
De Aguiar Luis Kluwe
Setti Princia Grejo
Borra Ricardo Carneiro
|
|
|
Abstract
|
|
|
|
Recently a screen from a library of 1.8 million compounds identified in vitro a potent activity of the 2-aminobenzimidazoles series against Leishmania infantum, the etiological agent responsible by over 20.000 deaths each year. Several analogs were synthesized and in vitro tested through an optimization program, leading to a promising 2-aminobenzimidazoles derived compound (2amnbzl-d) that was progressed to in vivo mice studies. However, the not expected toxic effects prevented its progression to more advanced preclinical and clinical phases of drug development. Due to limitations of cell models in detecting whole organism complex interactions, 90% of the compounds submitted to pre-clinical tests are reproved. The use of Zebrafish embryo models could improve this rate, saving mammals, time and costs in the development of new drugs. To test this hypothesis, we compared 2amnbzl-d with two compounds with already established safety profile: carbamazepine and benznidazole, using an embryo Zebrafish platform based on acute toxicity, hepatotoxicity, neurotoxicity and cardiotoxicity assays (Pltf-AcHpNrCd).
|
|
|
KEYWORD
|
|
|
3Rs, Animal health, Human health, Immunity, Leishmaniose, Toxicology
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
 
|
|