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
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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-2
H-isoindol-2-yl)methyl nitrate (
1); (1,3-dioxo-1,3-dihydro-2
H-isoindol-2-yl)ethyl nitrate (
2); 3-(1,3-dioxo-1,3-dihydro-2
H-iso-indol-2-yl)benzyl nitrate (
3); 4-(1,3-dioxo-1,3-dihydro-2
H-isoindol-2-yl)-
N-hydroxy-benzenesulfonamide (
4); 4-(1,3-dioxo-1,3-dihydro-2
H-isoindol-2-yl)benzyl nitrate (
5) and 2-[4-(1,3-dioxo-1,3-dihydro-2
H-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.
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