Bisphosphonates Inhibit the Growth ofTrypanosomabrucei,Trypanosomacruzi,Leishmaniadonovani,Toxoplasmagondii, andPlasmodiumfalciparum: A Potential Route to Chemotherapy
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- 16 February 2001
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 44 (6) , 909-916
- https://doi.org/10.1021/jm0002578
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 IC50 activity values against parasite replication (e.g. o-risedronate, IC50 = 220 nM for T. brucei rhodesiense; risedronate, IC50 = 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.Keywords
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