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Renes de Resende Machadohttp://lattes.cnpq.br/7206273812378648Márcio de Matos CoelhoCaryne Margotto BertolloJose Eduardo Gonçalveshttps://lattes.cnpq.br/1613923612602385Sarah Olivia Alves Mendes da Costa2023-09-28T13:34:44Z2023-09-28T13:34:44Z2020-08-21http://hdl.handle.net/1843/58978Modificações das estruturas químicas de substâncias com potencial terapêutico representam uma estratégia promissora no desenvolvimento de novos fármacos. A curcumina, um polifenol natural abundante no rizoma da Curcuma longa, é empregada na medicina tradicional devido às suas propriedades terapêuticas, principalmente anti-inflamatória. Em virtude da baixa biodisponibilidade da curcumina, análogos de curcumina foram sintetizados na tentativa de obter melhorias em características biofarmacêuticas e aumentar os efeitos biológicos. No presente estudo, avaliamos as atividades do análogo de curcumina.((2E,3E)-3-buten-2-ona-4-(4-hidroxi-3-metoxifenil)-2-(4-(4- metoxifenil )-2-tiazolil)hidrazona; RI75) em modelos de dores nociceptiva, inflamatória e neuropática e modelo de inflamação aguda em camundongos. A administração intraperitoneal (i.p.) prévia do RI75 (40 mg/kg) reduziu a alodínia mecânica induzida por carragenina ou paclitaxel. Entretanto, o RI75 não alterou a latência no modelo de resposta nociceptiva induzida por calor. A atividade motora dos animais não foi alterada pela administração do RI75. A atividade antinociceptiva do RI75 foi inibida pela administração prévia de naltrexona (5 ou 10 mg/kg, i.p) ou ciproheptadina (5 ou 10 mg/kg, i.p.), mas não de glibenclamida (20 ou 40 mg/kg, per os). O pré-tratamento com o RI75 (20 ou 40 mg/kg, i.p.) reduziu o edema de pata, a produção de fator de necrose tumoral-α e interleucina-6 e a atividade da mieloperoxidase induzidos por carragenina. Concluindo, os resultados do presente estudo demonstraram a atividade do análogo de curcumina RI75 em modelos de dores inflamatória e neuropática e de inflamação. A atividade do RI75 está relacionada com a ativação de mecanismos opioidérgicos e serotoninérgicos e a redução da produção de citocinas e do recrutamento de leucócitos. Os resultados podem servir como base para a realização de ensaios pré-clínicos para a avaliação da toxicidade e do perfil farmacocinético, etapas fundamentais para o avanço de pesquisas visando ao desenvolvimento de novas alternativas farmacoterapêuticas.Modifications of the chemical structures of substances with therapeutic potential represent a promising alternative aiming drug development. Curcumin is a major polyphenol isolated from the rhizome of turmeric (Curcuma longa) and widely used in traditional medicine due to its therapeutic properties, mainly antiinflammatory. Due to curcumin low bioavailability, curcumin analogues have been synthesized in an attempt to improve in biopharmaceutical characteristics and increase the biological effects. In the present study, we investigated the activity of a curcumin analogue ((2E,3E)-3-buten-2-one-4-(4-hydroxy-3methoxyphenyl )-2-(4-(4-methoxyphenyl)-2-thiazolyl)hydrazone; RI75) in models of nociceptive, inflammatory and neuropathic pain and acute inflammation in mice. Previous intraperitoneal (i.p.) administration of RI75 (40 mg/kg) reduced the mechanical allodynia induced by carrageenan or paclitaxel. However, RI75 did not change the latency in the model of nociceptive response induced by heat. The animal motor activity was not altered by the administration of RI75. The antinociceptive activity of the RI75 was inhibited by previous administration of naltrexone (5 or 10 mg/kg, i.p.) or cyproheptadine (5 or 10 mg/kg, i.p.), but not glibenclamide (20 or 40 mg/kg, per os). Pretreatment with RI75 (20 or 40 mg/kg, i.p.) reduced paw edema, tumor necrosis factor-α and interleukin 6 production and myeloperoxidase activity induced by carrageenan. In conclusion, the results of the present study demonstrate the activity of RI75 in models of inflammatory and neurophatic pain and inflammation. The activity of RI75 is associated with activation of the opioidergic and serotoninergic pathways and reduction of cytokines production and leukocyte recruitment. The results pave the way to further pre-clinical assays to evaluate the toxicological and pharmacokinetic profiles, essential steps aiming the development of new pharmacotherapeutic alternatives.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Ciências FarmacêuticasUFMGBrasilFARMACIA - FACULDADE DE FARMACIACurcuminaAnálogos de curcumina(2E,3E)-3-buten-2-ona-4- (4-hidroxi-3-metoxifenil)-2-(4-(4-metoxifenil)-2-tiazolil)hidrazonaRI75DorInflamaçãoCitocinasAtividades do (2E,3E)-3-buten-2-ona-4-(4-hidroxi-3- metoxifenil)-2-(4-(4-metoxifenil)-2-tiazolil)hidrazona, um análogo da curcumina, em modelos de dor e inflamação.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALDissertação RI75 SARAH (1).pdfDissertação RI75 SARAH (1).pdfapplication/pdf1042404https://repositorio.ufmg.br/bitstream/1843/58978/1/Disserta%c3%a7%c3%a3o%20RI75%20SARAH%20%281%29.pdf5b1032c423206e737cc645a55d80af1eMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/58978/2/license.txtcda590c95a0b51b4d15f60c9642ca272MD521843/589782023-09-28 10:34:45.24oai:repositorio.ufmg.br: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ório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-09-28T13:34:45Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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