JAC Advance Access originally published online on November 1, 2002
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Journal of Antimicrobial Chemotherapy (2002) 50, 975-980
© 2002 The British Society for Antimicrobial Chemotherapy
Evaluation of in vitro and in vivo activity of benzindazole-4,9-quinones against Cryptosporidium parvum
1 Freie Universität Berlin, Institut für Pharmazie, Pharmazeutische Technologie, Biopharmazie und Biotechnologie, Kelchstraße 31, 12169 Berlin; 5 Georg August-Universität Göttingen, Institut für Organische Chemie, Tammannstraße 2, 35077 Göttingen; 6 Robert Koch-Institut, Abteilung für Infektionskrankheiten, Nordufer 20, 13353 Berlin, Germany; 2 National Animal Disease Center, Agricultural Research Services, United States Department of Agriculture, Ames, IA 50010; 3 Kansas State University, Biology Department, Ackert Hall, Manhattan, KS 66506-4901; 4 Wadsworth Center, Division of Infectious Diseases, David Axelrod Institute for Public Health, Albany, NY 12201-2002, USA
Received 5 November 2001; returned 22 March 2002; revised 17 May 2002; accepted 8 August 2002
A series of benzindazole-4,9-quinones was tested for growth-inhibitory effects on Cryptosporidium parvum in vitro and in vivo. Most compounds showed considerable activity at concentrations from 25 to 100 µM. For instance, at 25 µM the derivatives 5-hydroxy-8-chloro- N1-methylbenz[f]-indazole-4,9-quinone and 5-chloro-N2-methylbenz[f]indazole-4,9-quinone in-hibited growth of C. parvum 78–100%, and at 50 µM seven of the 23 derivatives inhibited growth 
90%. The activity of the former two compounds was confirmed in a T-cell receptor 
(TCR-)-deficient mouse model of chronic cryptosporidiosis. In these mice, the mean infectivity scores (IS) in the caecum were 0.63–0.20, whereas in sham-treated mice the score was 1.44 (P < 0.05). There were similar differences in IS in the ileum, where the score for treated mice was 1.12–0.20 and that for mice receiving no drug was 1.32. There was no acute or chronic toxicity for any compound tested in vivo.
Keywords: naphthoquinones, benzindazole-4,9-quinones, Cryptosporidium, in vitro, in vivo, antiprotozoal, cytotoxicity, drug testing
* Corresponding author. Tel: +49-30-838-50689; Fax: +49-30-838-50616; E-mail: kayser{at}zedat.fu-berlin.de
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