In vitro efficacy of nitro- and bromo-thiazolyl-salicylamide compounds (thiazolides) against Besnoitia besnoiti infection in Vero cells

Cortes, H C E; Mueller, N; Esposito, M; Leitão, A; Naguleswaran, A; Hemphill, A (2007). In vitro efficacy of nitro- and bromo-thiazolyl-salicylamide compounds (thiazolides) against Besnoitia besnoiti infection in Vero cells. Parasitology, 134(Pt 7), pp. 975-85. London: Cambridge University Press 10.1017/S0031182007002417

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Nitazoxanide (NTZ) and its deacetylated metabolite tizoxanide (TIZ) exhibit considerable in vitro activity against Besnoitia besnoiti tachyzoites grown in Vero cells. Real-time-PCR was used to assess B. besnoiti tachyzoite adhesion, invasion, and intracellular proliferation in vitro. A number of NTZ-derivatives, including Rm4822 and Rm4803, were generated, in which the thiazole-ring-associated nitro-group was replaced by a bromo-moiety. We here show that replacement of the nitro-group on the thiazole ring with a bromo (as it occurs in Rm4822) does not impair the efficacy of the drug, but methylation of the salicylate ring at the ortho-position in a bromo-derivative (Rm4803) results in complete abrogation of the antiparasitic activity. Treatment of extracellular B. besnoiti tachyzoites with NTZ has an inhibitory effect on host cell invasion, while treatments with TIZ, Rm4822 do not. TEM demonstrates that the effects of Rm4822 treatment upon the parasites are similar to the damage induced by NTZ. This includes increased vacuolization of the parasite cytoplasm, and loss of the structural integrity of the parasitophorous vacuole and its membrane. Thus, Rm4822, due to the absence of a potentially mutagenic nitro-group, may represent an important potential addition to the anti-parasitic arsenal for food animal production, especially in cattle.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology

UniBE Contributor:

Müller, Norbert; Esposito, Marco; Naguleswaran, Arunasalam and Hemphill, Andrew

ISSN:

0031-1820

Publisher:

Cambridge University Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:54

Last Modified:

26 Oct 2019 12:40

Publisher DOI:

10.1017/S0031182007002417

PubMed ID:

17306057

Web of Science ID:

000248138900007

BORIS DOI:

10.7892/boris.22738

URI:

https://boris.unibe.ch/id/eprint/22738 (FactScience: 36376)

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