Lemos, Telma Maria Araujo MouraDantas, Luzia Leiros de Sena Fernandes Ribeiro2020-11-302020-11-302019-02-28DANTAS, Luzia Leiros de Sena Fernandes Ribeiro. Estudo in vivo da toxicidade e das atividades anti-inflamatória e antinociceptiva do (z)-2-(5-cloro-2-oxoindolin-3-ilideno)-n-fenilhidrazinacarbotioamida: um derivado de isatinatiossemicarbazona. 2019. 100f. Tese (Doutorado em Desenvolvimento e Inovação Tecnológica em Medicamentos) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2019.https://repositorio.ufrn.br/handle/123456789/30791The non-clinical study is a primordial step of the research and development process of new drugs, ensuring the safe use and the efficacy in humans. The isatin derivatives have aroused interest for their diversity of biological activities (antiviral, antibacterial, antitumor, anti-inflammatory, analgesic, etc.), with the possibility of being models of new therapeutic agents. So, the aim of this study was to evaluate, in vivo, the toxicity and the anti-inflammatory and antinociceptive activities of the isatinthiosemicarbazone (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenylhydrazinecarbothioamide or PA-Int6. Swiss mice of both sexes were used to evaluate three doses of this compound, administered by gavage: 1.0 mg/Kg (Test 1); 2.5 mg/Kg (Test 2) and 5.0 mg/Kg (Test 3). A prior assessment of central neural activity was made through the Open Field and Rotarod tests. Toxicity assays (acute and subchronic) performed were based on OECD protocols (Nos. 423, 407 and 408). In order to evaluate the anti-inflammatory activity were used the carrageenaninduced paw edema model and the zymosan-induced air pouch model. For the antinociceptive activity, the formalin test and the acetic acid-induced abdominal writhing test were used. Impairment on locomotor activity and coordination of animals treated with PA-Int6 (5.0 mg/Kg) has not been demonstrated. During the toxicity assays, there were no deaths or physical and behavioral changes. In the acute toxicity, no hematological parameter presented any difference, whereas the increase of Triglyceride for males was the only biochemical alteration. In subchronic toxicity few biochemical parameters had increased values among males (Albumin and Total Proteins) and among females (Triglyceride and Albumin). In addition, histopathological analysis of liver tissue showed extramedullary hematopoiesis in Test 2 and Test 3 groups, which was absent in the Control group.. The paw edema test demonstrated that since the first time evaluated all test groups showed inflammatory edema below 50%, but in the second and fourth hour they had significant responses. On induced inflammation by the airbag model there was decrease both in the leukocyte migration (55%, 50% and 47%) as in the protein extravasation (71%, 58% and 71%) for the three doses, respectively. Antinomyciceptive activity was observed for the three doses in the second phase of the formalin test, with reduction of paw pain time of 73.61% (Test 1), 79.46% (Test 2) and 73.85% (Test 3 ). The number of abdominal writhes decreased with increasing dose of PA-Int-6, but only with 5.0 mg/kg there was a significant response, reducing 24.88%. Thus, the results of this study suggest that PA-Int6 is safe, because it has demonstrated few and slight alterations, which can be physiologically reversed. With anti-inflammatory and antinociceptive activities, this compound can be considered promising, with the prospect of following in the research and development process as a candidate for a new drugAcesso AbertoToxicidade; Isatina; Tiosemicarbazona; Inflamação; Nocicepção;doctoralThesis