Mutagenicity of new lead compounds to treat sickle cell disease symptoms in a Salmonella/microsome assay.
Int J Mol Sci
; 11(2): 779-88, 2010 Feb 25.
Article
em En
| MEDLINE
| ID: mdl-20386668
ABSTRACT
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/micromol. These results allowed us to propose that a methyl spacer linked to a nitrate ester subunit associated to meta aromatic substitution decreases mutagenicity.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ftalimidas
/
Salmonella typhimurium
/
Microssomos Hepáticos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article