Assessment of the In Vivo Genotoxicity of New Lead Compounds to Treat Sickle Cell Disease

Autor(es)

dos Santos, Jean Leandro ^[1] ; Bosquesi, Priscila Longhin ^[1] ; Varanda, Eliana Aparecida ^[1] ; Lima, Lidia Moreira ^[2] ; Chung, Man Chin ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista UNESP, Lab Pesquisa & Desenvolvimento Farmacos Lapdesf, Dept Farmacos & Med, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP - Brazil

^[2] Univ Estadual Paulista UNESP, Dept Ciencias Biol, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 16, n. 4, p. 2982-2989, APR 2011.
• Citações Web of Science: 0

Resumo

The compounds 1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) methyl nitrate (C1), (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) ethyl nitrate (C2), 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (C3), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (C4), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (C5), and 2-{[}4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) phenyl] ethyl nitrate (C6) were evaluated with a micronucleus test using mouse peripheral blood to identify new candidate drugs for the treatment of sickle cell disease (SCD) that are safer than hydroxyurea. The compounds induced an average frequency of micronucleated reticulocytes (MNRET) of less than six per 1,000 cells at 12.5, 25, 50, and 100 mg/kg, whereas hydroxyurea induced an average MNRET frequency of 7.8, 9.8, 15, and 33.7 per 1000 cells respectively, at the same concentrations. Compounds C1-C6 are new non-genotoxic in vivo candidate drugs for the treatment of SCD symptoms. (AU)

• Processo FAPESP: 10/12495-6 - Otimização, síntese e avaliação farmacológica de novos candidatos a fármacos para tratamento dos sintomas da anemia falciforme
• Beneficiário: Jean Leandro dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular