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Int. J. Mol. Sci. 2010, 11(2), 779-788; doi:10.3390/ijms11020779
Communication

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

1,* , 2, 3 and 1
1 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 2 Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Univ Estadual Paulista–UNESP, Rodovia Araraquara Jaú Km. 01, 14801-902, Araraquara, SP, Brazil 3 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
(This article belongs to the Section Bioinorganic Chemistry)
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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 AMES test; mutagenicity; sickle cell; phthalimide derivatives
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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