Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay

Autor(es)

dos Santos, Jean Leandro ^[1] ; Varanda, Eliana A. ^[2] ; Lima, Lidia Moreira ^[3] ; Chin, Chung Man ^[1]

Afiliação do(s) autor(es)

^[1] UNESP, Fac Ciencias Farmaceut, Dept Farmacos & Medicamentos, Lapdesf, BR-14801902 Araraquara, SP - Brazil

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

^[3] UFRJ, Fac Farm, LASSBio, Ctr Ciencias Saude, BR-21944190 Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 11, n. 2, p. 779-788, FEB 2010.
• Citações Web of Science: 8

Resumo

A series of phthalimide derivatives planned as drugs candidates to treat the symptoms of sickle cell anemia were evaluated in a mutagenicity test using strains of Salmonella typhimurium TA100 and TA102, without and with addition of S9 mixture, with the aim to identify the best structural requirements for a drug candidate without genotoxic activity. The compounds (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl nitrate (1); (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl nitrate (2); 3-(1,3-dioxo-1,3-dihydro-2H-iso-indol-2-yl)benzyl nitrate (3); 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (4); 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) benzyl nitrate (5) and 2-{[}4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]ethyl nitrate (6) presented mutagenic potency ranging between 0-4,803 revertants/mu mol. These results allowed us to propose that a methyl spacer linked to a nitrate ester subunit associated to meta aromatic substitution decreases mutagenicity. (AU)

• Processo FAPESP: 07/56115-0 - Otimização, síntese e avaliação farmacológica de compostos híbridos duais úteis para o tratamento dos sintomas da anemia falciforme
• Beneficiário: Jean Leandro dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado