Avaliação da toxicidade não clínica in vivo do derivado da isatina 2-(3-hidroxi-2-oxoindolin-3-il) acrilonitrila (isacn) em modelo de caenorhabditis elegans

Abstract

Organic synthesis has become essential for the development of new drugs, allowing the creation of complex molecules with diverse therapeutic properties. Advances in medicinal chemistry have revolutionized pharmacology, and in this context, one of the highlights are heterocyclic compounds, which are structures that are easily amenable to chemical modifications, allowing the insertion of organic groups for a wide variety of purposes. Among them, isatin derivatives stand out as promising candidates for new drugs, which already have different pharmacological activities reported in the literature. Preliminary studies, such as toxicity tests, are essential for the development of new drug candidate molecules, ensuring safety for possible testing in humans. Thus, alternative models such as Caenorhabditis elegans have gained relevance for optimizing costs and reducing the number and use of animals. This nematode, with a short life cycle and wide distribution, shares 60-80% of human genes, many related to diseases, making it ideal for toxicological research. Thus, the present study aimed to evaluate the toxicity of the isatin derivative 2-(3-hydroxy-2-oxoindolin-3-yl)acrylonitrile (ISACN) using this animal model, following study methodologies defined for this species. Therefore, by evaluating some parameters, it was possible to conclude that the ISACN derivative did not reduce the hatching rate of C. elegans eggs, nor was it able to alter the quantification of pharyngeal beats, a parameter that is related to the nematode's feeding capacity. After treatment with the highest concentration tested, it was possible to observe an increase in the animal's motility pattern. Finally, it was not possible to observe changes in the body development tests and morphological analysis of the animals treated with the isatin derivative, concluding that the substance has low toxicity, at the concentrations tested, against the nematode. Corroborating previous studies by our research group, where the in vivo toxicity of this derivative was evaluated and it received a GHS 4 classification, indicating low toxicity.