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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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Yamasaki, Paulo Renato [1] ; do Nascimento, Dejair Caetano [2] ; Chelucci, Rafael Consolin [1] ; Fernandes Belone, Andrea de Faria [2] ; Rosa, Patricia Sammarco [2] ; Diorio, Suzana Madeira [2] ; Ferreira de Melo, Thais Regina [1] ; Barbieri, Karina Pereira [1] ; Polesi Placeres, Marisa Campos [1] ; Carlos, Iracilda Zepone [1] ; Chung, Man Chin [1] ; dos Santos, Jean Leandro [1]
Total Authors: 12
Affiliation:
[1] Univ Estadual Paulista UNESP, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP - Brazil
[2] Inst Laura Souza Lima, BR-17034971 Bourn, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Bioorganic & Medicinal Chemistry Letters; v. 24, n. 14, p. 3084-3087, JUL 15 2014.
Web of Science Citations: 6
Abstract

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. (AU)

FAPESP's process: 12/50359-2 - Design, synthesis and pharmacological evaluation of new hybrid drugs useful to treat hematological disorders
Grantee:Jean Leandro dos Santos
Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE