Publicação: Synthesis and evaluation of novel dapsone-thalidomide hybrids for the treatment of type 2 leprosy reactions
Nenhuma Miniatura disponível
Data
2014-07-15
Orientador
Coorientador
Pós-graduação
Curso de graduação
Título da Revista
ISSN da Revista
Título de Volume
Editor
Elsevier B.V.
Tipo
Artigo
Direito de acesso
Acesso restrito
Resumo
We synthesized a series of novel dapsone-thalidomide hybrids (3a-i) by molecular hybridization and evaluated their potential for the treatment of type 2 leprosy reactions. All of the compounds had analgesic properties. Compounds 3c and 3h were the most active antinociceptive compounds and reduced acetic acid-induced abdominal constrictions by 49.8% and 39.1%, respectively. The hybrid compounds also reduced tumor necrosis factor-alpha levels in lipopolysaccharide-stimulated L929 cells. Compound 3i was the most active compound; at concentrations of 15.62 and 125 mu M, compound 3i decreased tumor necrosis factor-alpha levels by 86.33% and 87.80%, respectively. In nude mice infected with Mycobacterium leprae in vivo, compound 3i did not reduce the number of bacilli compared with controls. Compound 3i did not have mutagenic effects in Salmonella typhimurium strains TA100 and TA102, with or without metabolic activation (S9 mixture). Our results indicate that compound 3i is a novel lead compound for the treatment of type 2 leprosy reactions. (C) 2014 Elsevier Ltd. All rights reserved.
Descrição
Palavras-chave
Idioma
Inglês
Como citar
Bioorganic & Medicinal Chemistry Letters. Oxford: Pergamon-elsevier Science Ltd, v. 24, n. 14, p. 3084-3087, 2014.
