1921
Volume 77, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

The activities of fosmidomycin derivatives, chloroquine, and pyrimethamine were assessed by the radioisotopic assay in clinical isolates of . In a series of experiments with RPMI 1640 medium–10% fetal bovine serum, the geometric mean 50% inhibitory concentrations (ICs) (n = 34) for fosmidomycin and FR900098 were 301 nM and 118 nM, respectively. In another series of experiments, the geometric mean ICs (n = 33) for fosmidomycin and TH II46 were 413 nM and 249 nM, respectively. The ICs were 2–3 times lower with RPMI–10% fetal bovine serum than the ICs obtained with RPMI–10% human serum. FR900098 and TH II46 were 2.6 and 1.7 times more potent, respectively, than fosmidomycin. There was no correlation between chloroquine or pyrimethamine and fosmidomycin, which suggested the absence of cross-resistance. Sequence analysis showed five amino acid substitutions, but their possible relationship with the response to fosmidomycin is not clear. Fosmidomycin derivatives are promising candidates for further development.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2007.77.214
2007-08-01
2017-09-21
Loading full text...

Full text loading...

/deliver/fulltext/14761645/77/2/0770214.html?itemId=/content/journals/10.4269/ajtmh.2007.77.214&mimeType=html&fmt=ahah

References

  1. Feagin JE, 1992. The 6 kb element of Plasmodium falciparum encodes mitochondrial cytochrome genes. Mol Biochem Parasitol 52 : 145–148.
  2. Wilson RJM, Denny PW, Preiser PR, Rangachari K, Roberts K, Roy A, Whyte A, Strath M, Moore DJ, Moore PW, Williamson DH, 1996. Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium falciparum. J Mol Biol 261 : 155–172.
  3. Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM, Fairlamb AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM, Subramanian GM, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW, Fraser CM, Barrell B, 2002. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419 : 498–511.
  4. Ralph SA, van Dooren GG, Waller RF, Crawford MJ, Fraunholz MJ, Foth BJ, Tonkin CJ, Roos DS, McFadden GI, 2004. Metabolic maps and functions of the Plasmodium falciparum apicoplast. Nat Rev Microbiol 2 : 203–216.
  5. Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Türbachova I, Eberl M, Zeidler J, Lichtenthaler HK, Soldati D, Beck E, 1999. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science 285 : 1573–1576.
  6. Wiesner J, Hintz M, Altincicek B, Sanderbrand S, Weidemeyer C, Beck E, Jomaa H, 2000. Plasmodium falciparum: detection of the deoxyxylulose 5-phosphate reductoisomerase activity. Exp Parasitol 96 : 182–186.
  7. Altincicek B, Kollas AK, Eberl M, Wiesner J, Sanderbrand S, Hintz M, Beck E, Jomaa H, 2001. LytB, a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli. FEBS Lett 499 : 37–40.
  8. Cassera MB, Gozzo FC, d’Alexandri FL, Merino EF, del Portillo HA, Peres VJ, Almeida IC, Eberlin MN, Wunderlich G, Wiesner J, Jomaa H, Kimura EA, Katzin AM, 2004. The methylerythritol phosphate pathway is functionally active in all intraerythrocytic stages of Plasmodium falciparum. J Biol Chem 279 : 51749–51759.
  9. Okuhara M, Kuroda Y, Goto T, Okamoto M, Terano H, Kohsaka M, Aoki H, Imanaka H, 1980. Studies on new phosphonic acid antibiotics. III. Isolation and characterization of FR-31564, FR-32863 and FR-33289. J Antibiot (Tokyo) 33 : 24–28.
  10. Kuemmerle HP, Murakawa T, Soneoka K, Konishi T, 1985. Fosmidomycin, a new phosphonic acid antibiotic. Part I: phase I tolerance studies. Int J Clin Pharmacol Ther Toxicol 23 : 515–520.
  11. Kuemmerle HP, Murakawa T, Sakamoto H, Sato N, Konishi T, de Santis F, 1985. Fosmidomycin, a new phosphonic acid antibiotic. Part II: 1. Human pharmacokinetics. 2. Preliminary early phase IIa clinical studies. Int J Clin Pharmacol Ther Toxicol 23 : 521–528.
  12. Missinou MA, Borrmann S, Schindler A, Issifou S, Adegnika AA, Matsiegui PB, Binder R, Lell B, Wiesner J, Baranek T, Jomaa H, Kremsner PG, 2002. Fosmidomycin for malaria. Lancet 360 : 1941–1942.
  13. Lell B, Ruangweerayut R, Wiesner J, Missinou MA, Schindler A, Baranek T, Hintz M, Hutchinson D, Jomaa H, Kremsner PG, 2003. Fosmidomycin, a novel chemotherapeutic agent for malaria. Antimicrob Agents Chemother 47 : 735–738.
  14. Borrmann S, Issifou S, Esser G, Adegnika AA, Ramharter M, Matsiegui PB, Oyakhirome S, Mawili-Mboumba DP, Missinou MA, Kun JFJ, Jomaa H, Kremsner PG, 2004. Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria. J Infect Dis 190 : 1534–1540.
  15. Borrmann S, Adegnika AA, Moussavou F, Oyakhirome S, Esser G, Matsiegui PB, Ramharter M, Lundgren I, Kombila M, Issifou S, Hutchinson D, Wiesner J, Jomaa H, Kremsner PG, 2005. Short-course regimens of artesunate-fosmidomycin in treatment of uncomplicated Plasmodium falciparum malaria. Antimicrob Agents Chemother 49 : 3749–3754.
  16. Borrmann S, Lundgren I, Oyakhirome S, Impouma B, Matsiegui PB, Adegnika AA, Issifou S, Kun JFJ, Hutchinson D, Wiesner J, Jomaa H, Kremsner PG, 2006. Fosmidomycin plus clindamycin for treatment of pediatric patients aged 1 to 14 years with Plasmodium falciparum malaria. Antimicrob Agents Chemother 50 : 2713–2718.
  17. Okuhara M, Kuroda Y, Goto T, Okamoto M, Terano H, Kohsaka M, Aoki H, Imanaka H, 1980. Studies on new phosphonic acid antibiotics. I. FR-900098, isolation and characterization. J Antibiot (Tokyo) 33 : 13–17.
  18. Mount DL, Nahlen BL, Patchen LC, Churchill FC, 1989. Adaptations of the Saker-Solomons test: simple, reliable colorimetric field assays for chloroquine and its metabolites in urine. Bull World Health Organ 67 : 295–300.
  19. Desjardins RE, Canfield CJ, Haynes JD, Chulay JD, 1979. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother 16 : 710–718.
  20. Basco LK, Ndounga M, Keundjian A, Ringwald P, 2002. Molecular epidemiology of malaria in Cameroon. IX. Characteristics of recrudescent and persistent Plasmodium falciparum infections after chloroquine or amodiaquine treatment in children. Am J Trop Med Hyg 66 : 117–123.
  21. Basco LK, 2003. Molecular epidemiology of malaria in Cameroon. XVI. Longitudinal surveillance of in vitro pyrimethamine resistance. Am J Trop Med Hyg 69 : 174–178.
  22. Basco LK, 2003. Molecular epidemiology of malaria in Cameroon. XVII. Baseline monitoring of atovaquone-resistant Plasmodium falciparum by in vitro drug assays and cytochrome b gene sequence analysis. Am J Trop Med Hyg 69 : 179–183.
  23. Basco LK, Ringwald P, 2007. Molecular epidemiology of malaria in Cameroon. XXIV. Trends of in vitro antimalarial drug responses in Yaoundé, Cameroon. Am J Trop Med Hyg 76 : 20–26.
  24. Wiesner J, Henschker D, Hutchinson DB, Beck E, Jomaa H, 2002. In vitro and in vivo synergy of fosmidomycin, a novel antimalarial drug, with clindamycin. Antimicrob Agents Chemother 46 : 2889–2894.
  25. Haemers T, Wiesner J, Van Poecke S, Goeman J, Henschker D, Beck E, Jomaa H, van Calenbergh S, 2006. Synthesis of α-substituted fosmidomycin analogues as highly potent Plasmodium falciparum growth inhibitors. Bioorg Med Chem Lett 16 : 1888–1891.
  26. Basco LK, 2006. Molecular epidemiology of malaria in Cameroon. XXIII. Experimental studies on serum substitutes and alternative culture media for in vitro drug sensitivity assays using clinical isolates of Plasmodium falciparum. Am J Trop Med Hyg. 75 : 777–782.
  27. Basco LK, 2003. Molecular epidemiology of malaria in Cameroon. XV. Experimental studies on serum substitutes and supplements and alternative culture media for in vitro drug sensitivity assays using fresh isolates. Am J Trop Med Hyg 69 : 168–173.
  28. Basco LK, 2003. Molecular epidemiology of malaria in Cameroon. XVII. Baseline monitoring of atovaquone-resistant Plasmodium falciparum by in vitro drug assays and cytochrome b gene sequence analysis. Am J Trop Med Hyg 69 : 179–183.
  29. Reuter K, Sanderbrand S, Jomaa H, Wiesner J, Steinbrecher I, Beck E, Hintz M, Klebe G, Stubbs MT, 2002. Crystal structure of 1-deoxy-D-xylulose-5-phosphate reductoisomerase, a crucial enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. J Biol Chem 277 : 5378–5384.
  30. Steinbacher S, Kaiser J, Eisenreich W, Huber R, Bacher A, Rohdich F, 2003. Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-d-erythritol 4-phosphate synthase (IspC). J Biol Chem 278 : 18401–18407.
  31. Yajima S, Hara K, Sanders JM, Yin FL, Ohsawa K, Wiesner J, Jomaa H, Oldfield E, 2004. Crystallographic structures of two bisphosphonate:1-deoxyxylulose-5-phosphate reducto-isomerase complexes. J Am Chem Soc 126 : 10824–10825.
  32. MacSweeney A, Lange R, Fernandes RP, Schulz H, Dale GE, Douangamath A, Proteau PJ, Oefner C, 2005. The crystal structure of E. coli 1-deoxy-D-xylulose-5-phosphate reducto-isomerase in a ternary complex with the antimalarial compound fosmidomycin and NADPH reveals a tight-binding closed enzyme conformation. J Mol Biol 345 : 115–127.
  33. Reichenberg A, Wiesner J, Weidemeyer C, Dreiseidler E, Sanderbrand S, Altincicek B, Beck E, Schlitzer M, Jomaa H, 2001. Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activity. Bioorg Med Chem Lett 11 : 833–835.
  34. Ortmann R, Wiesner J, Reichenberg A, Henschker D, Beck E, Jomaa H, Schlitzer M, 2005. Alkoxycarbonyloxyethyl ester prodrugs of FR900098 with improved in vivo antimalarial activity. Arch Pharm Chem Life Sci 338 : 305–314.
  35. Devreux V, Wiesner J, Goeman JL, van der Eycken J, Jomaa H, van Calenbergh S, 2006. Synthesis and biological evaluation of cyclopropyl analogues of fosmidomycin as potent Plasmodium falciparum growth inhibitors. J Med Chem 49 : 2656–2660.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2007.77.214
Loading
/content/journals/10.4269/ajtmh.2007.77.214
Loading

Data & Media loading...

  • Received : 03 Sep 2006
  • Accepted : 24 Apr 2007

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error