In Search of Novel Agents for Therapy of Tropical Diseases and Human Immunodeficiency Virus
2008-01-24T00:00:00Z (GMT) by
Malaria, sleeping sickness, Chagas’ disease, Aleppo boil, and AIDS are among the tropical diseases causing millions of infections and cases of deaths per year because only inefficient chemotherapy is available. Since the targeting of the enzymes of the polyamine pathway may provide novel therapy options, we aimed to inhibit the deoxyhypusine hydroxylase, which is an important step in the biosynthesis of the eukaryotic initiation factor 5A. In order to identify new lead compounds, piperidines were produced and biologically evaluated. The 3,5-diethyl piperidone-3,5-dicarboxylates <b>11</b> and <b>13</b> substituted with 4-nitrophenyl rings in the 2 and 6 positions were found to be active against <i>Trypanosoma brucei brucei</i> and <i>Plasmodium falciparum</i> combined with low cytotoxicity against macrophages. The corresponding monocarboxylates are only highly active against the <i>T. brucei brucei.</i> The piperidine oximether <b>53</b> demonstrated the highest plasmodicidal activity. Moreover, compounds <b>11</b> and <b>53</b> were also able to inhibit replication of HIV-1.