Synthesis and evaluation of novel dapsone-thalidomide hybrids for the treatment of type 2 leprosy reactions.

Autor: Yamasaki PR; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista-UNESP, Rodovia Araraquara Jaú Km 01, 14801-902 Araraquara, SP, Brazil., do Nascimento DC; Instituto Lauro de Souza Lima, Rodovia Comandante João Ribeiro de Barros, Km 225/226, 17034-971 Bauru, SP, Brazil., Chelucci RC; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista-UNESP, Rodovia Araraquara Jaú Km 01, 14801-902 Araraquara, SP, Brazil., de Faria Fernandes Belone A; Instituto Lauro de Souza Lima, Rodovia Comandante João Ribeiro de Barros, Km 225/226, 17034-971 Bauru, SP, Brazil., Rosa PS; Instituto Lauro de Souza Lima, Rodovia Comandante João Ribeiro de Barros, Km 225/226, 17034-971 Bauru, SP, Brazil., Diório SM; Instituto Lauro de Souza Lima, Rodovia Comandante João Ribeiro de Barros, Km 225/226, 17034-971 Bauru, SP, Brazil., de Melo TR; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista-UNESP, Rodovia Araraquara Jaú Km 01, 14801-902 Araraquara, SP, Brazil., Barbieri KP; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista-UNESP, Rodovia Araraquara Jaú Km 01, 14801-902 Araraquara, SP, Brazil., Placeres MC; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista-UNESP, Rodovia Araraquara Jaú Km 01, 14801-902 Araraquara, SP, Brazil., Carlos IZ; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista-UNESP, Rodovia Araraquara Jaú Km 01, 14801-902 Araraquara, SP, Brazil., Chung MC; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista-UNESP, Rodovia Araraquara Jaú Km 01, 14801-902 Araraquara, SP, Brazil., dos Santos JL; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista-UNESP, Rodovia Araraquara Jaú Km 01, 14801-902 Araraquara, SP, Brazil. Electronic address: santosjl@fcfar.unesp.br.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2014 Jul 15; Vol. 24 (14), pp. 3084-7. Date of Electronic Publication: 2014 May 16.
DOI: 10.1016/j.bmcl.2014.05.017
Abstrakt: 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-α levels in lipopolysaccharide-stimulated L929 cells. Compound 3i was the most active compound; at concentrations of 15.62 and 125 μM, compound 3i decreased tumor necrosis factor-α 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.
(Copyright © 2014 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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