Avaliação da atividade antinociceptiva e anti-inflamatória de novos derivados sintéticos de 4-aminoquinolina

• Autor(a) principal: Silva, Suellen Maria Albuquerque da
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal de Alagoas (UFAL)
• Texto Completo: http://www.repositorio.ufal.br/handle/riufal/5343
• topic: Cloroquina; Medição da dor; Nociceptividade; Anti-inflamatórios; 4-aminoquinolina; Chloroquine; Pain Measurement; Nociception; Anti-Inflamamatory agents; 4-aminoquinoline; CNPQ::CIENCIAS DA SAUDE::FARMACIA

The high prevalence of diseases that cause pain and inflammation, in addition to long-term therapies that cause many adverse effects, has encouraged the development of new substances with analgesic and anti-inflammatory actions. Pharmacological treatment usually consists of non-steroidal anti-inflammatory drugs (NSAIDs), steroidal anti-inflammatory drugs (EAIs), immunosuppressants, and biological and synthetic disease-modifying drugs (DMDs). Chloroquine, a 4-aminoquinoline included in the DMDs, is already used in the treatment of inflammatory diseases, such as malaria, systemic and discoid lupus erythematosus, sarcoidosis, and rheumatoid arthritis. Considering the need for new alternatives in the treatment of pain and inflammation, this study aimed to investigate the antinociceptive and anti-inflammatory potential of four new synthetic derivatives of 4-aminoquinoline (DS4AMQs), developed by the Catalysis and Chemical Reactivity Group – GCAR/IQB/UFAL. For the in vivo models, Swiss mice (n = 6), adults, both sexes, with 25-35 g, from the Central Animal Facility of the UFAL were used. The following toxicological tests were performed to assess the toxicity of DS4AMQs: in vitro toxicity test by the MTT method and in vivo oral acute toxicity test. The formalin-induced nociception assay was performed for dose screening. Acute anti-inflammatory activity was assessed by the Zymosan-induced peritonitis assay. The evaluation of antinociceptive activity was performed through the acetic acid-induced writhing test, glutamate-induced nociception test and hot plate test. Finally, the motor performance evaluation was conducted by the rotarod test. All the tests were performed in the Laboratory of Pharmacology and Immunity (LaFi/ICBS/UFAL). In the MTT assay, 0.1, 1 e 10 μM concentrations of all four DS4AMQs did not show signs of cytotoxicity; only in the 100 μM concentration, DS4AMQ1, DS4AMQ2, and DS4AMQ3 demonstrated cellular toxicity. In in vivo toxicology test, the estimated LD50s were: DS4AMQ1 and DS4AMQ2, 112,95 mg/kg; DS4AMQ3 > 175 mg/kg; DS4AMQ4, 232,95 mg/kg. In the formalin-induced nociception test, the 50 mg/kg dose statistically reduced the evaluated parameter in the inflammatory phase in all animals treated with DS4AMQ1, DS4AMQ2, and DS4AMQ3; the treatment with DS4AMQ4 did not present a statistically decrease. Thus, the following tests were conducted only with the derivatives that presented statistical results. In the Zymosan-induced peritonitis test, results showed a significant decrease in total number of recruited leukocytes, with an inhibition percentage between 88% and 92% for the tested DS4AMQs, and in the cytokine dosage the DS4AMQs statistically reduced IL-6 and statistically increased IL-10. In the acetic acid-induced writhing test, all DS4AMQs statically decrease the number of writhes, presenting an inhibition percentage between 71% and 77%; while in the glutamate-induced nociception test, the tested derivatives statistically reduced the nociceptive parameter, presenting an inhibition percentage between 53% and 68%. All tested DS4AMQs were able to statistically reduce the latency time in the hot plate test and were not able to affect the motor performance of animals in the rotarod test. In view of the results, it is possible to affirm that the DS4AMQs induce an acute anti-inflammatory action, as well as a central and peripheral antinociceptive potential, without interfering in the motor performance of animals, corroborating the research of new analgesic and anti-inflammatory drugs.