Leishmania panamensis: Comparative inhibition of nuclear DNA topoisomerase II enzymes from promastigotes and human macrophages reveals anti-parasite selectivity of fluoroquinolones, flavonoids and pentamidine

Experimental Parasitology

Volumn 116, Issue 4, 2007, Pages 475-482

  Cortázar, Tania M ^a   Coombs, Graham H ^b   Walker, John ^a  

^a CENTRO INTERNACIONAL DE ENTRENAMIENTO E INVESTIGACIONES MÉDICAS CIDEIM   (Colombia)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

Bis benzimidazole; DNA topoisomerase II; Enzyme inhibition; Flavonoid; Fluoroquinolone; Leishmania panamensis; Pentamidine; Protoberberine

Indexed keywords

4 [5 (4 METHYL 1 PIPERAZINYL)[2,5' BI 1H BENZIMIDAZOL] 2' YL]PHENOL; CINOXACIN; CIPROFLOXACIN; CORALYNE; DIMINAZENE ACETURATE; DNA TOPOISOMERASE (ATP HYDROLYSING); ELLAGIC ACID; ENOXACIN; FLAVONOID; HOE 33342; LOMEFLOXACIN; NALIDIXIC ACID; NORFLOXACIN; OFLOXACIN; PENTAMIDINE; PIBENZIMOL; QUERCETIN; QUINOLINE DERIVED ANTIINFECTIVE AGENT; STIBOGLUCONATE SODIUM;

ANTIPROTOZOAL ACTIVITY; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG POTENCY; DRUG SELECTIVITY; HUMAN; HUMAN CELL; LEISHMANIA PANAMENSIS; MACROPHAGE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; ANTI-INFECTIVE AGENTS; ANTIPROTOZOAL AGENTS; CELL LINE; CELL NUCLEUS; CIPROFLOXACIN; DNA TOPOISOMERASES, TYPE II; ELLAGIC ACID; ENOXACIN; FLAVONOIDS; FLUOROQUINOLONES; HUMANS; INHIBITORY CONCENTRATION 50; LEISHMANIA GUYANENSIS; MACROPHAGES; PENTAMIDINE; QUERCETIN;

LEISHMANIA PANAMENSIS;

EID: 34249901033     PISSN: 00144894     EISSN: 10902449     Source Type: Journal    
DOI: 10.1016/j.exppara.2007.02.018     Document Type: Article

References (50)

1. Anderson V., Gootz T.D., and Osheroff N. Topoiosmerase IV catalysis and mechanism of quinolone action. Journal of Biological Chemistry 273 (1998) 17879-17885
2. Basselin M., Badet-Denisot M., and Robert-Gero M. Modification of kinetoplast DNA minicircle composition in pentamidine-resistant Leishmania. Acta Tropica 70 (1998) 43-61
3. Basselin M., and Robert-Gero M. Alterations in membrane fluidity, lipid metabolism, mitochondrial activity, and lipophosphoglycan expression in pentamidine resistant Leishmania. Parasitology Research 84 (1998) 78-83
4. Basselin M., Denise H., Coombs G.H., and Barrett M. Resistance to pentamidine in Leishmania mexicana involves exclusion of the drug from the mitochondrion. Antimicrobial Agents and Chemotherapy 46 (2002) 3731-3738
5. Bell C.A., Dykstra C.C., Naiman N.A., Cory M., Fairley T.A., and Tidwell R.R. Structure- activity studies of dicationically substituted bis-benzimidazoles against Giardia lamblia: correlation of antigiardial activity with DNA binding affinity and giardial topoisomerase II inhibition. Antimicrobial Agents and Chemotherapy 37 (1993) 2668-2673
6. Bianciardi P., Fasanella A., Foglia Manzillo V., Trotta T., Pagano A., Sorino S., Gradoni L., and Oliva G. The efficacy of enrofloxacin, alone or combined with metronidazole, in the therapy of canine leishmaniasis. Parasitology Research 93 (2004) 486-492
7. Bodley A.L., and Shapiro T.A. Molecular and cytotoxic effects of camptothecin, a topoisomerase I inhibitor, on trypanosomes and Leishmania. Proceedings of the National Academy of Sciences USA 92 (1995) 3726-3730
8. Bosque F., Milon G., Valderrama L., and Saravia N.G. Permissiveness of human monocytes and monocyte-derived macrophages to infection of promastigotes of Leishmania (Viannia) panamensis. Journal of Parasitology 84 (1998) 1250-1256
9. Burri C., Bodley A.L., and Shapiro T.A. Topoisomerases in kinetoplastids. Parasitology Today 12 (1996) 226-231
10. Chakraborty A.K., and Majumder H.K. Decatenation of kinetoplast DNA by an ATP-dependent DNA topoisomerase from the kinetoplastid hemoflagellate Leishmania donovani. Molecular and Biochemical Parasitology 26 (1987) 215-224
11. Chakraborty A.K., and Majumder H.K. Mode of action of pentavalent antimonials: specific inhibition of type I DNA topoisomerase of Leishmania donovani. Biochemical and Biophysical Research Communications 152 (1988) 605-611
12. Cheesman S.J. The topoisomerases of protozoan parasites. Parasitology Today 16 (2000) 277-281
13. Croft S.L., and Hogg J. Limited activity of bacterial topoisomerase inhibitors against Leishmania donovani and Trypanosoma cruzi amastigotes in vitro. Transactions of the Royal Society for Tropical Medicine and Hygiene 82 (1988) 856
14. Das A., Dasgupta A., Sharma S., Ghosh M., Sengupta T., Bandopadhyay S., and Majumder H. Characterization of the gene encoding type II DNA topoisomerase from Leishmania donovani: a key molecular target in antileishmanial therapy. Nucleic Acids Research 29 (2001) 1844-1851
15. De Koning H.P. Uptake of pentamidine in Trypanosoma brucei brucei is mediated by three distinct transporters: implications for cross-resistance with arsenicals. Molecular Pharmacology 59 (2001) 586-592
16. Dykstra C.C., McClernon D.R., Elwell L.P., and Tidwell R.R. Selective inhibition of topoisomerases from Pneumocystis carinii compared with that of topoisomerases from mammalian cells. Antimicrobial Agents and Chemotherapy 38 (1994) 1890-1898
17. Fox K., Sansom C., and Stevens M. Footprinting studies on the sequence-selective binding of pentamidine to DNA. FEBS Letters 266 (1990) 150-154
18. Hanke T., Ramiro M.J., Trigueros S., Roca J., and Larraga V. Cloning, functional analysis and post-transcriptional regulation of a type II DNA topoisomerase from Leishmania infantum. A new potential target for anti-parasite drugs. Nucleic Acids Research 31 (2003) 4917-4928
19. Herwaldt B.L. Leishmaniasis. Lancet 354 (1999) 1191-1199
20. Hooper D.C. Clinical applications of quinolones. Biochimica et Biophysica Acta 1400 (1998) 45-61
21. Jean-Moreno V., Rojas R., Goyeneche D., Coombs G.H., and Walker J. Leishmania donovani: differential activities of classical topoisomerase inhibitors and antileishmanials against parasite and host cells at the level of DNA topoisomerase I and in cytotoxicity assays. Experimental Parasitology 112 (2006) 21-30
22. Jha T.K., Sundar S., Thakur C.P., Bachmann P., Karbwang J., Fischer C., Voss A., and Berman J. Miltefosine, an oral agent for the treatment of Indian visceral leishmaniasis. New England Journal of Medicine 341 (1999) 1795-1800
23. Liu L.F. DNA topoisomerase poisons as antitumor drugs. Annual Review of Biochemistry 58 (1989) 351-375
24. Marquis J.-F., Drolet M., and Olivier M. Consequence of Hoechst 33342-mediated Leishmania DNA topoisomerase-I inhibition on parasite replication. Parasitology 126 (2003) 21-30
25. Marquis J.-F., Markhey D., LaVole E.J., and Olivier M. Effects of topoisomerases inhibitors protoberberine on Leishmania donovani growth, macrophage function and infection. Journal of Parasitology 89 (2003) 1040-1052
26. Mittra B., Saha A., Chowdhury A., Pal C., Mandal S., Mukhopadhyay S., Bandyopadhyay S., and Majumder H. Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis. Molecular Medicine 6 (2000) 527-541
27. Montalban C., Martinez-Fernandez R., Calleja J.L., Garcia-Diaz J.D., Rubio R., Dronda F., Moreno S., Yebra M., Barros C., Cobo J., et al. Visceral leishmaniasis (kala-azar) as an opportunistic infection in patients infected with the human immunodeficiency virus in Spain. Review of Infectious Diseases 11 (1989) 655-660
28. Morrissey I., and George J. Activities of fluoroquinolones against Streptomyces pneumoniae type II topoisomerases purified as recombinant proteins. Antimicrobial Agents and Chemotherapy 43 (1999) 2579-2585
29. Nenortas E., Burri C., and Shapiro T. Antitrypanosomal activity of fluoroquinolones. Antimicrobial Agents and Chemotherapy 43 (1999) 2066-2068
30. Nenortas E., Kulikowicz T., Burri C., and Shapiro T. Antitrypanosomal activities of fluoroquinolones with pyrrolidinyl substitutions. Antimicrobial Agents and Chemotherapy 47 (2003) 3015-3017
31. Palacios R., Osorio L.E., Grajales L.F., and Ochoa M.T. Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimoniate for cutaneous leishmaniasis due to Leishmania Viannia species. American Journal of Tropical Medicine and Hygiene 64 (2001) 187-193
32. Pan X.S., and Fisher M. Streptococcus pneumoniae DNA gyrase and topoisomerase IV: over- expression, purification and differential inhibition by fluoroquinolones. Antimicrobial Agents and Chemotherapy 43 (1999) 1129-1136
33. Ramagli L.S., and Rodriguez L.V. Quantitation of microgram amounts of protein in two-dimensional polyacrylamide gel electrophoresis sample buffer. Electrophoresis 6 (1985) 559-563
34. Ray S., Hazra B., Mittra B., Das A., and Majumder H.K. Diospyrin, a bisnapthoquinone: a novel inhibitor of type I DNA topoisomerase of Leishmania donovani. Molecular Pharmacology 54 (1998) 994-999
35. Rojas R., Valderrama L., and Saravia N.G. Resistance to antimony and treatment failure in human L. Viannia infection. American Journal of Tropical Medicine & Hygiene 71 (2004) 201-202
36. Romero I.C., Saravia N.G., and Walker J. Selective action of fluoroquinolones against intracellular amastigotes of Leishmania (Viannia) panamensis in vitro. Journal of Parasitology 91 (2005) 1474-1479
37. Savoia D., Biglino S., Cestaro A., and Zucca M. In vitro and in vivo activity of some fluoroquinolones on two Leishmania species. European Bulletin of Drug Research 2 (1993) 135-138
38. Shapiro T.A., Klein V.A., and Englund P.T. Drug-promoted cleavage of kinetoplast DNA minicircles: evidence for a type II topoisomerase activity in trypanosome mitochondria. Journal of Biological Chemistry 264 (1989) 4173-4178
39. Shapiro T., and Englund P. Selective cleavage of kinetoplast DNA minicircles promoted by antitrypanosomal drugs. Proceedings of the National Academy of Sciences USA 87 (1990) 950-954
40. Soto J., Arana B.A., Toledo J., Rizzo N., Vega J.C., Diaz A., Luz M., Gutierrez P., Arboleda M., Berman J.D., Junge K., Ángel J., and Sindermann H. Miltefosine for new world cutaneous leishmaniasis. Clinical Infectious Diseases 38 (2004) 1266-1272
41. Sundar S. Drug resistance in Indian visceral leishmaniasis. Tropical Medicine and International Health 6 (2001) 849-854
42. Sundstrom C., and Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). International Journal of Cancer 17 (1976) 565-577
43. Takei M., Fukuda H., Yasue T., Hosaka M., and Oomori Y. Inhibitory activities of gatifloxacin (AM-1155), a newly developed fluoroquinolone, against bacterial and mammalian type II topoisomerases. Antimicrobial Agents and Chemotherapy 42 (1998) 2678-2681
44. Trask D.K., and Muller M.T. Biochemical characterization of topoisomerase I purified from avian erythrocytes. Nucleic Acids Research 11 (1983) 2779-2800
45. Van Dross R.T., and Sanders M.M. Molecular characterization of recombinant Pneumocystis carinii topoisomerase I: differential interactions with human topoisomerase poisons and pentamidine. Antimicrobial Agents and Chemotherapy 46 (2002) 2145-2154
46. Velez I., Agudelo S., Hendrickx E., Puerta J., Grogl M., Modabber F., and Berman J. Inefficacy of allopurinol as monotherapy for Colombian cutaneous leishmaniasis: a randomized, controlled trial. Annals of Internal Medicine 26 (1997) 232-236
47. Villa H., Otero-Marcos A.R., Reguera R.M., Balana-Fouce R., Garcia-Estrada C., Perez-Pertejo Y., Tekwani B.L., Myler P.J., Stuart K.D., Bjornsti M.A., and Ordonez D. A novel active DNA topoisomerase I in Leishmania donovani. Journal of Biological Chemistry 278 (2003) 3521-3526
48. Walker J., and Saravia N.G. Inhibition of Leishmania donovani promastigote DNA topoisomerase I and human monocyte topoisomerases I and II by antimonial drugs and classical anti-topoisomerase agents. Journal of Parasitology 90 (2004) 1155-1162
49. WHO Report, 1999. Available from: .
50. WHO Fact Sheet No. 116, 2000. Available from: