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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #121993
Title: EVALUATION OF IN VITRO AND IN VIVO ACTIVITY OF NAPHTHINDAZOLE-4,9-QUINONES AGAINST CRYPTOSPORIDIUM PARVUM

Author
item KAYSER, OLIVER - BERLIN GERMANY
item Waters, Wade
item WOODS, KEITH - KANSAS STATE UNIV.
item UPTON, STEVE - KANSAS STATE UNIV.
item KEITHLY, JANET - WADSWORTH CENTER, NY
item LAATSCH, HARTMUT - BERLIN, GERMANY
item KIDERLEN, ALBRECHT - BERLIN, GERMANY

Submitted to: Antimicrobial Agents and Chemotherapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/12/2002
Publication Date: N/A
Citation: N/A

Interpretive Summary: Cryptosporidium parvum is an intestinal protozoan parasite that causes diarrheal disease in calves. This disease is costly to dairy and beef producers, and the disease can also spread to humans. Unfortunately, there are no effective drug treatments available for this parasite. In the present study, it was determined that naphthinadazol-4,9-quinone is effective at inhibiting the in vitro growth of Cryptosporidium parvum. These compounds also diminished Cryptosporidium parvum infection of immune deficient mice. Further study of these compounds may lead to ways to treat Cryptosporidium parvum infection in calves, thus reducing economic losses to producers and reducing the risk of human disease through exposure to sick calves.

Technical Abstract: A series of naphthindazole-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 uM. For instance at 25 uM 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 uM 7 of the 23 derivatives inhibited growth (90%). The activity of the former two compounds was confirmed in a TCR-(-deficient mouse model of chronic cryptosporidiosis which mimics the disease in AIDS patients. In these mice, the mean infectivity scores in (IS) the caecum were 0.63-0.20 whereas in sham-treated mice the score was 0.81 (p=0.05). Similar differences in IS were noted in the ileum where the score for treated mice was 1.12-0.20 compared to 1.25 in mice receiving no drug. There was no acute or chronic toxicity for any compound tested in vivo.