title: Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy.
abstract: We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC(50) activity values against parasite replication (e.g. o-risedronate, IC(50) = 220 nM for T. brucei rhodesiense; risedronate, IC(50) = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.
authors: Departments of Chemistry and Biophysics, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
authors: M B
authors: MB
authors: Martin
authors: J S
authors: JS
authors: Grimley
authors: J C
authors: JC
authors: Lewis
authors: H T
authors: HT
authors: Heath
authors: B N
authors: BN
authors: Bailey
authors: H
authors: H
authors: Kendrick
authors: V
authors: V
authors: Yardley
authors: A
authors: A
authors: Caldera
authors: R
authors: R
authors: Lira
authors: J A
authors: JA
authors: Urbina
authors: S N
authors: SN
authors: Moreno
authors: R
authors: R
authors: Docampo
authors: S L
authors: SL
authors: Croft
authors: E
authors: E
authors: Oldfield
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004164:Diphosphonates / Q000494:pharmacology*; D007893:Leishmania donovani / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D014122:Toxoplasma / Q000187:drug effects; D014346:Trypanosoma brucei brucei / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects; D014709:Vero Cells
chemical_list: D000981:Antiprotozoal Agents; D004164:Diphosphonates