novobiocin and Trypanosomiasis--African

novobiocin has been researched along with Trypanosomiasis--African* in 1 studies

Other Studies

1 other study(ies) available for novobiocin and Trypanosomiasis--African

ArticleYear
Potent antitrypanosomal activities of heat shock protein 90 inhibitors in vitro and in vivo.
    The Journal of infectious diseases, 2013, Aug-01, Volume: 208, Issue:3

    African sleeping sickness, caused by the protozoan parasite Trypanosoma brucei, is universally fatal if untreated, and current drugs are limited by severe toxicities and difficult administration. New antitrypanosomals are greatly needed. Heat shock protein 90 (Hsp90) is a conserved and ubiquitously expressed molecular chaperone essential for stress responses and cellular signaling. We investigated Hsp90 inhibitors for their antitrypanosomal activity. Geldanamycin and radicicol had nanomolar potency in vitro against bloodstream-form T. brucei; novobiocin had micromolar activity. In structure-activity studies of geldanamycin analogs, 17-AAG and 17-DMAG were most selective against T. brucei as compared to mammalian cells. 17-AAG treatment sensitized trypanosomes to heat shock and caused severe morphological abnormalities and cell cycle disruption. Both oral and parenteral 17-DMAG cured mice of a normally lethal infection of T. brucei. These promising results support the use of inhibitors to study Hsp90 function in trypanosomes and to expand current clinical development of Hsp90 inhibitors to include T. brucei.

    Topics: Animals; Antiprotozoal Agents; Benzoquinones; Disease Models, Animal; Enzyme Inhibitors; Female; HSP90 Heat-Shock Proteins; Lactams, Macrocyclic; Macrolides; Mice; Novobiocin; Structure-Activity Relationship; Treatment Outcome; Trypanosoma brucei brucei; Trypanosomiasis, African

2013