No abstract

It has been more than 25 years since it was first reported that nifurtimox and benznidazole promote superoxide production in trypanosomes. However, there has been no direct evidence of an association between the drug-induced free radicals and trypanocidal activity. Here, we identify a superoxide dismutase required to protect Trypanosoma brucei from drug-generated superoxide.

Design and Synthesis of Bioactive Adamantane Spiro Heterocycles. -Spiro adamantanes are synthesized to examine their anti-influenza A virus properties and trypanocidal activities, and to correlate their potency to the size of the heterocyclic ring. Two main characteristics arise from this examination: i) moving from six-to four-to a three-membered ring reduces the activity both against influenza A virus and T. brucei; ii) nonsubstituted heterocyclic compounds are more active, whereas N-methylation causes a drastic reduction in potency. Spiro compounds (I) and (II) exhibit potent anti-influenza A virus activity. Piperidine derivative (II), endowed with the most potent activity, is 12-fold more active than amantadine, about 2-fold more active than rimantadine, and 54-fold more potent than ribavirin. It is also the most active compound against blood-stream forms of T. brucei. -(KOLOCOURIS*, N.; ZOIDIS, G.; FOSCOLOS, G. B.; FYTAS, G.; PRATHALINGHAM, S. R.; KELLY, J. M.; NAESENS, L.; DE CLERCQ, E.; Bioorg. Med. Chem. Lett. 17 (2007) 15, 4358-4362; Dep. Pharm. Chem., Univ. Athens, GR-15771 Athens, Greece; Eng.) -H. Hoennerscheid 47-209