In Search of Novel Agents for Therapy of Tropical Diseases and Human Immunodeficiency Virus Tim Goebel Daniela Ulmer Holger Projahn Jessica Kloeckner Eberhard Heller Melanie Glaser Alicia Ponte-Sucre Sabine Specht Salem Ramadan Sarite Achim Hoerauf Annette Kaiser Ilona Hauber Joachim Hauber Ulrike Holzgrabe 10.1021/jm070763y.s001 https://acs.figshare.com/articles/journal_contribution/In_Search_of_Novel_Agents_for_Therapy_of_Tropical_Diseases_and_Human_Immunodeficiency_Virus/2961199 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. 2008-01-24 00:00:00 6 positions AIDS plasmodicidal activity compounds 11 piperidine oximether 53 Plasmodium falciparum deoxyhypusine hydroxylase Tropical Diseases novel therapy options Novel Agents Human Immunodeficiency VirusMalaria HIV brucei brucei eukaryotic initiation factor 5 polyamine pathway Trypanosoma brucei brucei