Evaluation of in vitro and in vivo activity of benzindazole-4,9-quinones against Cryptosporidium parvum

Abstract

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-N 1 -methylbenz[f]-indazole-4,9-quinone and 5-chloro-N 2 -methylbenz[f]indazole-4,9-quinone inhibited 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 α (TCR-α)-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

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