- Synthesis and in vitro trypanocidal activity of some novel iron chelating agents
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This report describes the syntheses and in vitro trypanocidal activity of a number of iron(III) chelators against epimastigotes of Trypanosoma cruzi. The compounds examined included a number of lipophilic N-alkyl derivatives of 2-ethyl- and 2-methyl-3-hydroxypyrid-4-ones, N,N'-bis(o-hydroxybenzyl)-(±)-trans-1,2-diaminocyclohexane, cyclotetrachromotropylene and four commercially available carboxy derivatives of pyridine, pyrazine, and pyarazole. Benznidazole, the drug clinically used in the treatment of Chagas' disease in humans, served as standard. All compounds were screened in vitro against Trypanosoma cruzi epimastigotes at 50 and 100 μg/ml for 72 h of exposure. At 100 μg/ml dosage, at least 4 compounds exhibited high epimastigote growth inhibition (65-69%) comparable to benznidazole (72%), whereas 9 compounds showed moderate to fair activity (53-64%) in the in vitro assay. At the lower concentration (50 μg/ml), the inhibitory activity of the best of these compounds was reduced significantly (39-48%) compared to the standard drug (59%). The activity of all the carboxylic acids remained in the lower range (4-25%). It is hypothesized that the enhanced activity of some of the compounds is due to their increased lipophilicity which enables them to successfully pass through the cellular membrane of Trypanosoma cruzi epimastigotes. The trypanocidal activities of the most effective compounds were significantly reduced when tested in the presence of added ferric ion.
- Singh, Pramod K.,Jones, Mark M.,Lane, Joshua E.,Nesset, Anna,Zimmerman, Lisa J.,Ribeiro-Rodrigues, Rodrigo,Richter, Ashley,Stenger, Michael R.,Carter, Clint E.
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p. 311 - 315
(2007/10/03)
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- Stabilization of organic compounds
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Admixture of insulin and a hydroxypyridone being: (1) a 3-hydroxypyrid-4-one in which the hydrogen atom attached to the nitrogen atom is replaced by an aliphatic acyl group, by an aliphatic hydrocarbon group, or by an aliphatic hydrocarbon group substituted by one or more substituents selected from aliphatic acyl, alkoxy, cycloalkoxy, aliphatic amide, aliphatic ester, halogen and hydroxy groups and, optionally, in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by an aliphatic acyl, alkoxy, cycloalkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, by an aliphatic hydrocarbon group, or by an aliphatic hydrocarbon group substituted by an alkoxy, cycloalkoxy, aliphatic ester, halogen or hydroxy group, or a salt thereof.
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- Process for producing pyrid-4-ones
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Substituted-3-hydroxy-pyrid-4-ones, derivatives thereof, and salts thereof are produced by reacting subsituted-3-hydroxypyr-4-one with ammonia or a non-sterically hindered primary amine usually in the presence of a solvent such as water. Also disclosed are novel derivatives of 2-ethyl-3-hydroxypyrid-4-one.
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