In Search of Novel Agents for Therapy of Tropical Diseases and Human Immunodeficiency Virus
Autor: | Jessica Kloeckner, Joachim Hauber, Alicia Ponte-Sucre, Daniela Ulmer, Ulrike Holzgrabe, Melanie Glaser, Ilona Hauber, Tim Goebel, Achim Hoerauf, Holger Projahn, Salem Ramadan Sarite, Eberhard Heller, Annette Kaiser, Sabine Specht |
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Rok vydání: | 2007 |
Předmět: |
Anti-HIV Agents
Plasmodium falciparum Trypanosoma brucei brucei Trypanosoma brucei Virus Replication Virus Cell Line Antimalarials Mice Structure-Activity Relationship Piperidines Eukaryotic initiation factor Oximes parasitic diseases Drug Discovery medicine Animals Humans Spiro Compounds Leishmania major biology Macrophages Kinetoplastida Tropical disease Deoxyhypusine Hydroxylase medicine.disease biology.organism_classification Trypanocidal Agents Virology Anti-Bacterial Agents Mice Inbred C57BL HIV-1 Molecular Medicine Malaria Ethers |
Zdroj: | Journal of Medicinal Chemistry. 51:238-250 |
ISSN: | 1520-4804 0022-2623 |
DOI: | 10.1021/jm070763y |
Popis: | 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 11 and 13 substituted with 4-nitrophenyl rings in the 2 and 6 positions were found to be active against Trypanosoma brucei brucei and Plasmodium falciparum combined with low cytotoxicity against macrophages. The corresponding monocarboxylates are only highly active against the T. brucei brucei. The piperidine oximether 53 demonstrated the highest plasmodicidal activity. Moreover, compounds 11 and 53 were also able to inhibit replication of HIV-1. |
Databáze: | OpenAIRE |
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