(31)P NMR of apicomplexans and the effects of risedronate on Cryptosporidium parvum growth.
High-resolution 303.6 MHz (31)P NMR spectra have been obtained of perchloric acid extracts of Plasmodium berghei trophozoites, Toxoplasma gondii tachyzoites, and Cryptosporidium parvum oocysts. Essentially complete resonance assignments have been made based on chemical shifts and by coaddition of authentic reference compounds. Signals corresponding to inorganic pyrophosphate were detected in all three species. In T. gondii and C. parvum, additional resonances were observed corresponding to linear triphosphate as well as longer chain polyphosphates. Spectra of P. berghei and T. gondii also indicated the presence of phosphomonoesters and nucleotide phosphates. We also report that the pyrophosphate analog drug, risedronate (used in bone resorption therapy), inhibits the growth of C. parvum in a mouse xenograft model. When taken together, our results indicate that all the major disease-causing apicomplexan parasites contain extensive stores of condensed phosphates and that as with Plasmodium falciparum and T. gondii, the pyrophosphate analog drug risedronate is an inhibitor of C. parvum cell growth.
Moreno
B
B
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
Bailey
B N
BN
Luo
S
S
Martin
M B
MB
Kuhlenschmidt
M
M
Moreno
S N
SN
Docampo
R
R
Oldfield
E
E
D000818:Animals; D000977:Antiparasitic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003457:Cryptosporidiosis / Q000188:drug therapy*; D016785:Cryptosporidium parvum / Q000737:chemistry*; D011756:Diphosphates / Q000032:analysis; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D010761:Phosphorus Radioisotopes; D010962:Plasmodium berghei / Q000737:chemistry*; D011817:Rabbits; D000068296:Risedronic Acid; D014122:Toxoplasma / Q000737:chemistry*; D014183:Transplantation, Heterologous
D000977:Antiparasitic Agents; D011756:Diphosphates; D010761:Phosphorus Radioisotopes; D000068296:Risedronic Acid; D012968:Etidronic Acid