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Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay
Lapdesf–Laboratório de Pesquisa e Desenvolvimento de Fármacos, Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas, Univ Estadual Paulista–UNESP, Rodovia Araraquara Jaú Km. 01, 14801-902, Araraquara, SP, Brazil
Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Univ Estadual Paulista–UNESP, Rodovia Araraquara Jaú Km. 01, 14801-902, Araraquara, SP, Brazil
LASSBio–Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Univ Federal do Rio de Janeiro–UFRJ, Centro de Ciências da Saúde, Cidade Universitária, Ilha do Fundão, 21.944-190–Rio de Janeiro, RJ, Brazil
* Author to whom correspondence should be addressed.
Received: 15 January 2010 / Accepted: 10 February 2010 / Published: 25 February 2010
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/μmol. These results allowed us to propose that a methyl spacer linked to a nitrate ester subunit associated to meta aromatic substitution decreases mutagenicity.
Keywords: AMES test; mutagenicity; sickle cell; phthalimide derivatives
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MDPI and ACS Style
Dos Santos, J.L.; Varanda, E.A.; Lima, L.M.; Chin, C.M. Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay. Int. J. Mol. Sci. 2010, 11, 779-788.
Dos Santos JL, Varanda EA, Lima LM, Chin CM. Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay. International Journal of Molecular Sciences. 2010; 11(2):779-788.
Dos Santos, Jean Leandro; Varanda, Eliana A.; Lima, Lídia Moreira; Chin, Chung Man. 2010. "Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay." Int. J. Mol. Sci. 11, no. 2: 779-788.