Bisphosphonate inhibitors of Toxoplasma gondi growth: In vitro, QSAR, and in vivo investigations

Journal of Medicinal Chemistry

Volumn 48, Issue 9, 2005, Pages 3130-3140

  Ling, Yan ^a   Sahota, Gurmukh ^a   Odeh, Sarah ^a   Chan, Julian M W ^a   Araujo, Fausto G ^b   Moreno, Silvia N J ^a,c   Oldfield, Eric ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^b PALO ALTO MEDICAL FOUNDATION   (United States)

^c UNIVERSITY OF GEORGIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 DEOXYXYLULOSE 5 PHOSPHATE REDUCTOISOMERASE; ALENDRONIC ACID; ATOVAQUONE; BISPHOSPHONIC ACID DERIVATIVE; FOSMIDOMYCIN; GERANYLTRANSFERASE; HYDROCARBON; ISOMERASE; ISOPRENE; MEVALONIC ACID; NITROGEN; PAMIDRONIC ACID; PHOSPHONIC ACID DERIVATIVE; RISEDRONIC ACID; UNCLASSIFIED DRUG; ZOLEDRONIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOSYNTHESIS; COMPARATIVE MOLECULAR FIELD ANALYSIS; COMPARATIVE MOLECULAR SIMILARITY INDICES ANALYSIS; CONTROLLED STUDY; ELECTRICITY; ENZYME INHIBITION; FEMALE; GENETIC ENGINEERING; GROWTH INHIBITION; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; LD 50; MOUSE; NONHUMAN; OSTEOLYSIS; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STEREOCHEMISTRY; TOXOPLASMA GONDII; TOXOPLASMOSIS;

ALDOSE-KETOSE ISOMERASES; ALKYL AND ARYL TRANSFERASES; ANIMALS; ANTIPROTOZOAL AGENTS; CELL LINE; DIPHOSPHONATES; FOSFOMYCIN; GERANYLTRANSTRANSFERASE; HUMANS; MICE; MODELS, MOLECULAR; MULTIENZYME COMPLEXES; OXIDOREDUCTASES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; TOXOPLASMA; TOXOPLASMOSIS;

EID: 18244410156     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm040132t     Document Type: Article

References (46)

1. Martin, M. B.; Grimley, J. S.; Lewis, J. C.; Heath, H. T., 3rd; Bailey, B. N. et al. Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy. J. Med. Chem. 2001, 44, 909-916.
2. Yardley, V.; Khan, A. A.; Martin, M. B.; Slifer, T. R.; Araujo, F. G. et al. In vivo activities of farnesyl pyrophosphate synthase inhibitors against Leishmania donovani and Toxoplasma gondii. Antimicrob. Agents Chemother. 2002, 46, 929-931.
3. Rogers, M. J.; Watts, D. J.; Russell, R. G. Overview of bisphosphonates. Cancer 1997, 80, 1652-1660.
4. Martin, M. B.; Sanders, J. M.; Kendrick, H.; de Luca-Fradley, K.; Lewis, J. C. et al. Activity of bisphosphonates against Trypanosoma brucei rhodesiense. J. Med. Chem. 2002, 45, 2904-2914.
5. 31P NMR of apicomplexans and the effects of risedronate on Cryptosporidium parvum growth. Biochem. Biophys. Res. Commun. 2001, 284, 632-637.
6. Rodriguez, N.; Bailey, B. N.; Martin, M. B.; Oldfield, E.; Urbina, J. A. et al. Radical cure of experimental cutaneous leishmaniasis by the bisphosphonate pamidronate. J. Infect. Dis. 2002, 186, 138-140.
7. Garzoni, L. R.; Caldera, A.; Meirelles, M. N.; de Castro, S. L.; Docampo, R. et al. Selective in vitro effects of the farnesyl pyrophosphate synthase inhibitor risedronate on Trypanosoma cruzi. Int. J. Antimicrob. Agents 2004, 23, 273-285.
8. Garzoni, L. R.; Waghabi, M. C.; Baptista, M. M.; de Castro, S. L.; Meirelles, M. N. et al. Antiparasitic activity of risedronate in a murine model of acute Chagas' disease. Int. J. Antimicrob. Agents 2004, 23, 286-290.
9. Bergstrom, J. D.; Bostedor, R. G.; Masarachia, P. J.; Reszka, A. A.; Rodan, G. Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch. Biochem. Biophys. 2000, 375, 231-241.
10. Dunford, J. E.; Thompson, K.; Coxon, F. P.; Luckman, S. P.; Hahn, F. M. et al. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J. Pharmacol. Exp. Ther. 2001, 296, 235-242.
11. Grove, J. E.; Brown, R. J.; Watts, D. J. The intracellular target for the antiresorptive aminobisphosphonate drugs in Dictyostelium discoideum is the enzyme farnesyl diphosphate synthase. J. Bone Miner. Res. 2000, 15, 971-981.
12. Keller, R. K.; Fliesler, S. J. Mechanism of aminobisphosphonate action: characterization of alendronate inhibition of the isoprenoid pathway. Biochem. Biophys. Res. Commun. 1999, 266, 560-563.
13. van Beek, E.; Pieterman, E.; Cohen, L.; Lowik, C.; Papapoulos, S. Farnesyl pyrophosphate synthase is the molecular target of nitrogen- containing bisphosphonates. Biochem. Biophys. Res. Commun. 1999, 264, 108-111.
14. Montalvetti, A.; Bailey, B. N.; Martin, M. B.; Severin, G. W.; Oldfield, E. et al. Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase. J. Biol. Chem. 2001, 276, 33930-33937.
15. Das, H.; Wang, L.; Kamath, A.; Bukowski, J. F. Vgamma2Vdelta2 T-cell receptor-mediated recognition of aminobisphosphonates. Blood 2001, 98, 1616-1618.
16. Sanders, J. M.; Ghosh, S.; Chan, J. M.; Meints, G.; Wang, H. et al. Quantitative structure-activity relationships for γδ T cell activation by bisphosphonates. J. Med. Chem. 2004, 47, 375-384.
17. Kato, Y.; Tanaka, Y.; Miyagawa, F.; Yamashita, S.; Minato, N. Targeting of tumor cells for human gammadelta T cells by nonpeptide antigens. J. Immunol. 2001, 167, 5092-5098.
18. Kunzmann, V.; Bauer, E.; Feurle, J.; Weissinger, F.; Tony, H. P. et al. Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood 2000, 96, 384-392.
19. Wilhelm, M.; Kunzmann, V.; Eckstein, S.; Reimer, P.; Weissinger, F. et al. Gammadelta T cells for immune therapy of patients with lymphoid malignancies. Blood 2003, 102, 200-206.
20. Wang, L.; Kamath, A.; Das, H.; Li, L.; Bukowski, J. F. Antibacterial effect of human V gamma 2V delta 2 T cells in vivo. J. Clin. Invest. 2001, 108, 1349-1357.
21. Eberl, M.; Hintz, M.; Reichenberg, A.; Kollas, A. K.; Wiesner, J. et al. Microbial isoprenoid biosynthesis and human gammadelta T cell activation. FEBS Lett. 2003, 544, 4-10.
22. Jomaa, H.; Wiesner, J.; Sanderbrand, S.; Altincicek, B.; Weidemeyer, C. et al. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science 1999, 285, 1573-1576.
23. Testa, C. A.; Brown, M. J. The methylerythritol phosphate pathway and its significance as a novel drug target. Curr. Pharm. Biotechnol. 2003, 4, 248-259.
24. Szabo, C. M.; Matsumura, Y.; Fukura, S.; Martin, M. B.; Sanders, J. M. et al. Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents. J. Med. Chem. 2002, 45, 2185-2196.
25. Sanders, J. M.; Gomez, A. O.; Mao, J.; Meints, G. A.; Van Brussel, E. M. et al. 3-D QSAR investigations of the inhibition of Leishmania major farnesyl pyrophosphate synthase by bisphosphonates. J. Med. Chem. 2003, 46, 5171-5183.
26. Ghosh, S.; Chan, J. M.; Lea, C. R.; Meints, G. A.; Lewis, J. C. et al. Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo. J. Med. Chem. 2004, 47, 175-187.
27. Dobrowolski, J. M.; Sibley, L. D. Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite. Cell 1996, 84, 933-939.
28. Sigma Plot 5.0; SPSS Inc.: Chicago.
29. Soldati, D.; Boothroyd, J. C. Transient transfection and expression in the obligate intracellular parasite Toxoplasma gondii. Science 1993, 260, 349-352.
30. Araujo, F. G.; Khan, A. A.; Slifer, T. L.; Bryskier, A.; Remington, J. S. The ketolide antibiotics HMR 3647 and HMR 3004 are active against Toxoplasma gondii in vitro and in murine models of infection. Antimicrob. Agents Chemother. 1997, 41, 2137-2140.
31. SYBYL 6.9; Tripos Inc.: St. Louis.
32. Clark, M.; Cramer, R. D., 3rd; Van Opdenbosch, N. Validation of the General Purpose Tripos 5.2 Force Field. J. Comput. Chem. 1989, 10, 982-1012.
33. Powell, M. J. D. Restart procedures for the conjugate gradient method. Math. Programming 1977, 12, 241-254.
34. Press, W. H. Numerical recipes in C: the art of scientific computing; Cambridge University Press: New York, 1988; p 324.
35. Gasteiger, J.; Marsili, M. Iterative partial equalization of orbital electronegativity: a rapid access to atomic charges. Tetrahedron 1980, 36, 3219-3328.
36. Kotsikorou, E.; Oldfield, E. A quantitative structure-activity relationship and pharmacophore modeling investigation of aryl-X and heterocyclic bisphosphonates as bone resorption agents. J. Med. Chem. 2003, 46, 2932-2944.
37. Tarshis, L. C.; Proteau, P. J.; Kellogg, B. A.; Sacchettini, J. C.; Poulter, C. D. Regulation of product chain length by isoprenyl diphosphate synthases. Proc. Natl. Acad. Sci. 1996, 93, 15018-15023.
38. Bush, B. L.; Nachbar, R. B., Jr. Sample-distance partial least squares: PLS optimized for many variables, with application to CoMFA. J. Comput. Aided Mol. Des. 1993, 7, 587-619.
39. Cramer, R. D., 3rd; Patterson, D. E.; Bunce, J. D. Recent advances in comparative molecular field analysis (CoMFA). Prog. Clin. Biol. Res. 1989, 291, 161-165.
40. Klebe, G.; Abraham, U.; Mietzner, T. Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J. Med. Chem. 1994, 37, 4130-4146.
41. Montalvetti, A.; Fernandez, A.; Sanders, J. M.; Ghosh, S.; Van Brussel, E. et al. Farnesyl pyrophosphate synthase is an essential enzyme in Trypanosoma brucei. In vitro RNA interference and in vivo inhibition studies. J. Biol. Chem. 2003, 278, 17075-17083.
42. McFadden, D. C.; Tomavo, S.; Berry, E. A.; Boothroyd, J. C. Characterization of cytochrome b from Toxoplasma gondii and Q(o) domain mutations as a mechanism of atovaquone-resistance. Mol. Biochem. Parasitol. 2000, 108, 1-12.
43. Hosfield, D. J.; Zhang, Y.; Dougan, D. R.; Broun, A.; Tari, L. W. et al. Structural basis for bisphosphonate-mediated inhibition of isoprenoid biosynthesis. J. Biol. Chem. 2004, 279, 8526-8529.
44. Altincicek, B.; Hintz, M.; Sanderbrand, S.; Wiesner, J.; Beck, E. et al. Tools for discovery of inhibitors of the 1-deoxy-D-xylulose 5-phosphate (DXP) synthase and DXP reductoisomerase: an approach with enzymes from the pathogenic bacterium Pseudomonas aeruginosa. FEMS Microbiol. Lett. 2000, 190, 329-333.
45. Neu, H. C.; Kamimura, T. In vitro and in vivo antibacterial activity of FR-31564, a phosphonic acid antimicrobial agent. Antimicrob. Agents Chemother. 1981, 19, 1013-1023.
46. Khanna, S. C.; Green, J. Methanediphosphonic acid formulations with ion exchangers. U.S. Patent 5,344,825, 1994.