Study of Compounds for Activity against Leishmania

摘要

During this contract, a total of 205 selected compounds were studied for efficacyagainst Leishmania Leishmania donovani infections in hamsters. Forty-four of these compounds were active as indicated by 50 percent or greater parasite suppression. Glucantime Indices ranged from 1,418 to 0.351. Among these active compounds were 8-aminoquinolines (which are the most efficacious), phenanthrene methanols, dibenzopyrroles, disulfides, aminothiols, and C-nucleosides. When Glucantime, Pentostam or Amphotericin B were given in combination with the 8-aminoquinoline, WRO6026, antileishmanial efficacy was not enhanced significantly over that observed with WRO6026 alone. A total of 146 compounds were studied for efficacy against Leishmania Viannia braziliensis and 42 were active as indicated by 50 percent or greater suppression of Lesion area caused by these parasites. Glutucantime Indices for these active compounds ranged from 40.9 to 0.474. Generally, the most active compounds were 8-aminoquinolines. Many of these compounds were active when administered either orally or via the intramuscular routes. In addition, a phosphonium compound had some efficacy against Leishmania (V.) braziliensis as did Sinefungin. Both of these compounds are toxic. A total of 51 selected oligonucteotides were studied in vitro for antileishmanial activity against promastigotes of Leishmania (L.) donovani. Only one of these was noted to be active. Leishmania Leishmania donovani, Leishmania Viannia braziliensis, Chemotherapy, Sinefungin, Phosphoniums, 8-aminoquinolines, Oligonucleotides, Phenanthrene methanols, Trifluralin, Dibenzopyrroles.