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In vitro effects of arylimidamides against Besnoitia besnoiti infection in Vero cells

Published online by Cambridge University Press:  24 February 2011

H. C. E. CORTES
Affiliation:
Laboratório de Parasitologia Victor Caeiro, Núcleo da Mitra, ICAAM, Universidade de Évora, Apartado 94, 7000-554 Évora, Portugal
N. MULLER
Affiliation:
Institute of Parasitology, University of Berne, Längass-Strasse 122, CH-3012 Berne, Switzerland
D. BOYKIN
Affiliation:
Department of Chemistry, Georgia State University, PO Box 4098, Atlanta, Georgia 30302-4098, USA
C. E. STEPHENS
Affiliation:
Department of Chemistry and Physics, Augusta State University, Augusta, Georgia 30904-2200, USA
A. HEMPHILL*
Affiliation:
Institute of Parasitology, University of Berne, Längass-Strasse 122, CH-3012 Berne, Switzerland
*
*Corresponding author:Institute of Parasitology, University of Berne, Längass-Strasse 122, CH-3012 Berne, Switzerland. Tel: +41 31 631 2474. Fax: +41 31 631 2477. E-mail: hemphill@ipa.unibe

Summary

The in vitro effects of 4 arylimidamides (DB811, DB786, DB750 and DB766) against the proliferative tachyzoite stage of the apicomplexan parasite Besnoitia besnoiti were investigated. These four compounds had been shown earlier to exhibit in vitro activities in the nanomolar range against the related apicomplexans Neospora caninum and Toxoplasma gondii. Real-time-PCR was used to assess B. besnoiti intracellular proliferation in vitro. Preliminary assessment by light microscopy identified DB811 and DB750 as the most promising compounds, while DB786 and DB766 were much less effective. Three-day-growth assays and quantitative real-time PCR was used for IC50 determination of DB811 (0·079 μM) and DB750 (0·56 μM). Complete growth inhibition was observed at 1·6 μM for DB 811 and 1·7 μM for DB750. However, when infected cultures were treated for 14 days, proliferation of parasites occurred again in cultures treated with DB750 from day 4 onwards, while the proliferation of DB811-treated tachyzoites remained inhibited. Electron microscopy of B. besnoiti-infected fibroblast cultures fixed and processed at different time-points following the initiation of drug treatments revealed that DB811 exerted a much higher degree of ultrastructural alterations compared to DB750. These results show that arylimidamides such as DB811 could potentially become an important addition to the anti-parasitic arsenal for food animal production, especially in cattle.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2011

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References

REFERENCES

Batista, D. G. J., Batista, M. M., de Oliveira, G. M., do Amaral, P. B., Lannes-Vieira, J., Britto, C. C., Junqueira, A., Lima, M. M., Romanha, A. J., Sales, P. A. S, Stephend, C. E., Boykin, D. W. and Soeiro, M. N. C. (2010). Arylimidamide DB766, a potential chemotherapeutic candidate for Chagas’ disease treatment. Antimicrobial Agents and Chemotherapy 54, 29402954.CrossRefGoogle Scholar
Blagburn, B. L., Drain, K. L., Land, T. M., Kinard, R. G., Moore, P. H., Lindsay, D. S., Patrick, D. A., Boykin, D. W. and Tidwell, R. R. (1998 a). Comparative efficacy evaluation of dicationic carbazole compounds, nitazoxanide, and paromomycin against Cryptosporidium parvum infections in a neonatal mouse model. Antimicrobial Agents and Chemotherapy 42, 28772882.Google Scholar
Blagburn, B. L., Drain, K. L., Land, T. M., Moore, P. H., Kinard, R. G., Lindsay, D. S., Kumar, A., Shi, J., Boykin, D. W. and Tidwell, R. R. (1998 b). Dicationic furans inhibit development of Cryptosporidium parvum in HSD/ICR suckling Swiss mice. Journal of Parasitology 84, 851856.CrossRefGoogle ScholarPubMed
Bougdour, A., Braun, L., Cannella, D. and Hakimi, M. A. (2010). Chromatin modifications: implications in the regulation of gene expression in Toxoplasma gondii. Cellular Microbiology 12, 413423, doi:CMI1446 [pii];10.1111/j.1462-5822.2010.01446.x [doi].CrossRefGoogle ScholarPubMed
Bray, P. G., Barrett, M. P., Ward, S. A. and De Koning, H. P. (2003). Pentamidine uptake and resistance in pathogenic protozoa: past, present and future. Trends in Parasitology 19, 232239, doi:S1471492203000692 [pii].CrossRefGoogle ScholarPubMed
Cortes, H., Ferreira, M. L., Silva, J. F., Vidal, R., Serra, P. and Caeiro, V. (2003). Contribuição para o estudo da besnoitiose bovina em Portugal. Revista Portuguesa de Ciências Veterinárias 98, no. 545, 4346.Google Scholar
Cortes, H., Leitão, A., Vidal, R., Soares, H., Marques, I., Reis, Y., Waap, E., Pereira da Fonseca, I., Fazendeiro, I., Ferreira, M. L. and Caeiro, V. (2004). Identification, isolation and sequence variability of Besnoitia besnoiti in Portugal. Proceedings of COST Action 857, 1st Annual Workshop, May 3–6th, Lisbon, Portugal.Google Scholar
Cortes, H., Leitão, A., Vidal, R., Vila-Vicosa, M. J., Ferreira, M. L., Caeiro, V. and Hjerpe, C. A. (2005). Besnoitiosis in bulls in Portugal. Veterinary Record 157, 262264.CrossRefGoogle ScholarPubMed
Cortes, H. C., Mueller, N., Esposito, M., Leitao, A., Naguleswaran, A. and Hemphill, A. (2007 a). In vitro efficacy of nitro- and bromo-thiazolyl-salicylamide compounds (thiazolides) against Besnoitia besnoiti infection in Vero cells. Parasitology 111.Google ScholarPubMed
Cortes, H. C., Reis, Y., Gottstein, B., Hemphill, A., Leitao, A. and Muller, N. (2007 b). Application of conventional and real-time fluorescent ITS1 rDNA PCR for detection of Besnoitia besnoiti infections in bovine skin biopsies. Veterinary Parasitology 146, 352356.CrossRefGoogle ScholarPubMed
Cortes, H. C., Reis, Y., Waap, H., Vidal, R., Soares, H., Marques, I., Pereira, d. F. I., Fazendeiro, I., Ferreira, M. L., Caeiro, V., Shkap, V., Hemphill, A. and Leitao, A. (2006). Isolation of Besnoitia besnoiti from infected cattle in Portugal 2. Veterinary Parasitology 141, 226233.CrossRefGoogle Scholar
de Souza, E. M., Lansiaux, A., Bailly, C., Wilson, W. D., Hu, Q., Boykin, D. W., Batista, M. M., Araujo-Jorge, T. C. and Soeiro, M. N. (2004). Phenyl substitution of furamidine markedly potentiates its anti-parasitic activity against Trypanosoma cruzi and Leishmania amazonensis. Biochemical Pharmacology 68, 593600, doi:10.1016/j.bcp.2004.04.019 [doi];S0006295204003089 [pii].CrossRefGoogle ScholarPubMed
de Souza, E. M., Menna-Barreto, R., Araujo-Jorge, T. C., Kumar, A., Hu, Q., Boykin, D. W. and Soeiro, M. N. (2006). Antiparasitic activity of aromatic diamidines is related to apoptosis-like death in Trypanosoma cruzi. Parasitology 133, 7579, doi:S0031182006000084 [pii];10.1017/S0031182006000084 [doi].CrossRefGoogle ScholarPubMed
Elsheikha, H. M. and Mansfield, L. S. (2004). Determination of the activity of sulfadiazine against Besnoitia darlingi tachyzoites in cultured cells. Parasitology Research 93, 423426, doi:10.1007/s00436-004-1133-5 [doi].CrossRefGoogle ScholarPubMed
Esposito, M., Moores, S., Naguleswaran, A., Muller, J. and Hemphill, A. (2007 a). Induction of tachyzoite egress from cells infected with the protozoan Neospora caninum by nitro- and bromo-thiazolides, a class of broad-spectrum anti-parasitic drugs. International Journal for Parasitology 37, 11431152.CrossRefGoogle ScholarPubMed
Esposito, M., Muller, N. and Hemphill, A. (2007 b). Structure-activity relationships from in vitro efficacies of the thiazolide series against the intracellular apicomplexan protozoan Neospora caninum. International Journal for Parasitology 37, 183190.CrossRefGoogle ScholarPubMed
Esposito, M., Stettler, R., Moores, S. L., Pidathala, C., Muller, N., Stachulski, A., Berry, N. G., Rossignol, J. F. and Hemphill, A. (2005). In vitro efficacies of nitazoxanide and other thiazolides against Neospora caninum tachyzoites reveal antiparasitic activity independent of the nitro group. Antimicrobial Agents and Chemotherapy 49, 37153723.CrossRefGoogle ScholarPubMed
Fernandez-Garcia, A., Alvarez-Garcia, G., Risco-Castillo, V., Aguado-Martinez, A., Marcen, J. M., Rojo-Montejo, S., Castillo, J. A. and Ortega-Mora, L. M. (2010). Development and use of an indirect ELISA in an outbreak of bovine besnoitiosis in Spain. Veterinary Record 166, 818822, doi:166/26/818 [pii];10.1136/vr.b4874 [doi].CrossRefGoogle Scholar
Gollnick, N. S., Gentile, A. and Schares, G. (2010). Diagnosis of bovine besnoitiosis in a bull born in Italy. Veterinary Record 166, 599, doi:166/19/599 [pii];10.1136/vr.c2314 [doi].CrossRefGoogle Scholar
Gomez, C., Esther, R. M., Calixto-Galvez, M., Medel, O. and Rodriguez, M. A. (2010). Regulation of gene expression in protozoa parasites. Journal of Biomedical Biotechnology 2010, 726045, doi:10.1155/2010/726045.CrossRefGoogle ScholarPubMed
Gondim, L. F. (2006). Neospora caninum in wildlife. Trends in Parasitology 22, 247252.CrossRefGoogle ScholarPubMed
Hemphill, A., Vonlaufen, N., Naguleswaran, A., Keller, N., Riesen, M., Guetg, N., Srinivasan, S. and Alaeddine, F. (2004). Tissue culture and explant approaches to studying and visualizing Neospora caninum and its interactions with the host cell. Microscopy and Microanalysis 10, 602620.CrossRefGoogle ScholarPubMed
Jacquiet, P., Lienard, E. and Franc, M. (2010). Bovine besnoitiosis: Epidemiological and clinical aspects. Veterinary Parasitology, doi:S0304-4017(10)00454-1 [pii];10.1016/j.vetpar.2010.08.013 [doi].CrossRefGoogle ScholarPubMed
Juste, R. A., Cuervo, L. A., Marco, J. C. and Oregui, L. M. (1990). La besnoitiosis bovina: desconocida en España? Medicina Veterinária 7, 613618.Google Scholar
Kim, J. T., Park, J. Y., Seo, H. S., Oh, H. G., Noh, J. W., Kim, J. H., Kim, D. Y. and Youn, H. J. (2002). In vitro antiprotozoal effects of artemisinin on Neospora caninum. Veterinary Parasitology 103, 5363.CrossRefGoogle ScholarPubMed
Kwon, H. J., Kim, J. H., Kim, M., Lee, J. K., Hwang, W. S. and Kim, D. Y. (2003). Anti-parasitic activity of depudecin on Neospora caninum via the inhibition of histone deacetylase. Veterinary Parasitology 112, 269276.CrossRefGoogle ScholarPubMed
Leepin, A., Studli, A., Brun, R., Stephens, C. E., Boykin, D. W. and Hemphill, A. (2008). Host cells participate in the in vitro effects of novel diamidine analogues against tachyzoites of the intracellular apicomplexan parasites Neospora caninum and Toxoplasma gondii. Antimicrobial Agents and Chemotherapy 52, 19992008, doi:AAC.01236-07 [pii];10.1128/AAC.01236-07 [doi].CrossRefGoogle ScholarPubMed
Lindsay, D. S. and Dubey, J. P. (1989). Evaluation of anti-coccidial drugs’ inhibition of Neospora caninum development in cell cultures. Journal of Parasitology 75, 990992.CrossRefGoogle ScholarPubMed
Lindsay, D. S., Rippey, N. S., Cole, R. A., Parsons, L. C., Dubey, J. P., Tidwell, R. R. and Blagburn, B. L. (1994). Examination of the activities of 43 chemotherapeutic agents against Neospora caninum tachyzoites in cultured cells. American Journal of Veterinary Research 55, 976981.Google ScholarPubMed
Pols, J. W. (1960). Studies on Bovine besnoitiosis with special reference to the aetiology. Onderstepoort Journal of Veterinary Research 28, 265356.Google Scholar
Schares, G., Basso, W., Majzoub, M., Cortes, H. C., Rostaher, A., Selmair, J., Hermanns, W., Conraths, F. J. and Gollnick, N. S. (2009). First in vitro isolation of Besnoitia besnoiti from chronically infected cattle in Germany. Veterinary Parasitology 163, 315322, doi:S0304-4017(09)00276-3 [pii];10.1016/j.vetpar.2009.04.033 [doi].CrossRefGoogle ScholarPubMed
Shkap, V., de Waal, D. T. and Potgieter, F. T. (1985). Chemotherapy of experimental Besnoitia besnoiti infection in rabbits. Onderstepoort Journal of Veterinary Research 52, 289.Google ScholarPubMed
Shkap, V., Pipano, E. and Ungar-Waron, H. (1987). Besnoitia besnoiti: chemotherapeutic trials in vivo and in vitro. Revue d'Elevage et de Medecine Veterinaire des Pays Tropicaux 40, 259264.Google ScholarPubMed
Wang, M. Z., Zhu, X., Srivastava, A., Liu, Q., Sweat, J. M., Pandharkar, T., Stephens, C. E., Riccio, E., Parman, T., Munde, M., Mandal, S., Madhubala, R., Tidwell, R. R., Wilson, W. D., Boykin, D. W., Hall, J. E., Kyle, D. E. and Werbovetz, K. A. (2010). Novel arylimidamides for treatment of visceral leishmaniasis. Antimicrobial Agents and Chemotherapy 54, 25072516, doi:AAC.00250-10 [pii];10.1128/AAC.00250-10 [doi].CrossRefGoogle ScholarPubMed
Youn, H. J., Lakritz, J., Rottinghaus, G. E., Seo, H. S., Kim, D. Y., Cho, M. H. and Marsh, A. E. (2004). Anti-protozoal efficacy of high performance liquid chromatography fractions of Torilis japonica and Sophora flavescens extracts on Neospora caninum and Toxoplasma gondii. Veterinary Parasitology 125, 409414.CrossRefGoogle ScholarPubMed
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