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In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives
Journal article   Open access   Peer reviewed

In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives

S K Katiyar and T D Edlind
Antimicrobial agents and chemotherapy, v 41(12), pp 2729-2732
Dec 1997
PMID: 9420047
url
https://doi.org/10.1128/AAC.41.12.2729View
Published, Version of Record (VoR) Open

Abstract

Encephalitozoon - drug effects Animals Albendazole - metabolism Humans Vero Cells - parasitology Albendazole - pharmacology Cercopithecus aethiops Benzimidazoles - pharmacology AIDS-Related Opportunistic Infections - parasitology Encephalitozoonosis - drug therapy Albendazole - analogs & derivatives Antiprotozoal Agents - pharmacology
Recent reports have described the successful treatment of Encephalitozoon intestinalis infection in AIDS patients with albendazole. However, this compound is rapidly metabolized in vivo to albendazole sulfoxide, and furthermore it is only 1 of about 15 commercially developed benzimidazole derivatives. To compare the activities of albendazole, albendazole sulfoxide, and other benzimidazoles, an in vitro system involving infection of green monkey kidney cell (E6) monolayers with E. intestinalis spores was developed. After 14 days, the effects of benzimidazoles on spore production were determined. Ten of fourteen derivatives tested, including albendazole, were inhibitory at concentrations of 1 to 10 ng/ml. Derivatives modified at the 1 or 2 position were less active. Albendazole sulfoxide was 1.7-fold more inhibitory than albendazole but significantly less toxic to E6 cells, a finding that explains the clinical efficacy of this compound. Potential alternatives to albendazole are discussed. No albendazole-resistant E. intestinalis mutants were obtained following in vitro selection.

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Web of Science research areas
Microbiology
Pharmacology & Pharmacy
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