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

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 muM. For instance, at 25 muM 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 in-hibited growth of C. parvum 78-100%, and at 50 muM seven of the 23 derivatives inhibited growth greater than or equal to90%. The activity of the former two compounds was confirmed in a T-cell receptor alpha (TCR-alpha)-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.