Leishmania chagasi

Dietze R, Carvalho SF, Valli LC, Berman J, Brewer T, Milhous W, Sanchez J, Schuster B, Grogl M. Phase 2 trial of WR6026, an orally administered 8-aminoquinoline, in the treatment of visceral leishmaniasis caused by Leishmania chagasi. Am J Trop Med Hyg 2001 65(6) 685-9. 

FeSODs occurs also in plants (mainly in the chloroplasts) and are common in protozoa, e.g., Tetrahymena pyriformis. Entamoeba histolytica, Plasmodium falciparum, Leishmania chagasi. Trypanosoma cruzi and Trichomonas vaginalis. 

The sandfly Lutzomyia longipalpis is the vector of the protozoan parasite Leishmania chagasi, the causative agent of visceral leishmaniasis in South and Central America. Population control of L. longipalpis is therefore of urgent importance to prevent the disease. In 1994, Hamilton and coworkers isolated the male-produced pheromone of L. longipalpis from Jacobina, Brazil, and proposed its structure as 3-methyl-a-himachalene (96, Figure 4.47) with unknown stereochemistry. We first synthesized ( R, 3R, 1 S )-( )-96.81 Enantiomer separation (optical resolution) of a synthetic intermediate enabled us to prepare both the enantiomers of 96, and their bioassay and GC comparisons with the natural pheromone showed the latter to be (lS,3S,lR)-96. 

Slunt KM, Grace JM, Macdonald TL et al. Effect of mitonafide analogs on topoisomerase II of Leishmania chagasi. Antimicrob Agents Chemother 1996 40 706-709. 

Werbovetz KA, Spoors PG, Pearson RD et al. Cleavable complex formation in Leishmania chagasi treated with anilinoacridines. Mol Biochem Paiasitol 1994 65 1-10. 

SO Ismail, YAW Skeiky, A Bhatia, LA Omara-Opyene, L Gedamu. Molecular cloning, characterization, and expression in Escherichia coli of iron superoxide dismu-tase cDNA from Leishmania donovani chagasi. Infect Immun 62 657-664, 1994. 

A series of l,3,4-thiadiazolium-2-phenylamine derivatives (41-51) was studied in L. amazonensis. The cytotoxic effects of these compounds on the host cells were investigated and the antileishmanial in vitro activity was compared with other species of Leishmania (I. chagasi and I. braziliensis). The compounds presented lower toxicity in murine macrophages than the reference drug pentamidine. The halogen derivatives (4-F, 4-C1, 4-Br, and 3-C1) (44,47-49) were the most active compounds among all the species tested [83]. 

Structuie-acdvity relationship studies with mitonafide have revealed that the compound inhibits both nuclear and mitochondrial topoisomerase of Leishmania with preferential taiget-ing of the mitochondrial enzyme over the nuclear enzyme. Anilinoacridines have recently been found to possess andparasidc activity towards Leishmania, Trypanosoma and Plasmodium species. These compounds have been shown to induce protein associated DNA lesions in L. chagasi promastigotes. Linearization of kinteoplast DNA minicirdes have also been repotted in parasites treated with anilinoacridines at similar concentrations. Members of the 9-anilinoacridine topoisomerase II inhibitors have also been shown to inhibit growth of L. major promast otes and amastigotes. 9-aminoacridines, that are reported topoisomerase II inhibitors and structurally related to the antileishmanial compound quinacrine and chlorpro-mazine, have shown anti leishmanial activity at concentrations in the range of 10-20 pM. ... 

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