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Antimicrobial Agents and Chemotherapy, December 2003, p. 3853-3858, Vol. 47, No. 12
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.12.3853-3858.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Activity of 9-(S)-[3-Hydroxy-2-(Phosphonomethoxy)Propyl]Adenine against Schistosomiasis mansoni in Mice

Sanaa Botros,¹ Samia William,¹ Olfat Hammam,¹ Zdenek Zídek,^2* and Antonín Hol³

Theodor Bilharz Research Institute, Giza, Egypt,¹ Institute of Experimental Medicine,² Institute of Organic Chemistry and Biochemistry, Academy of Sciences of The Czech Republic, Prague, Czech Republic³

Received 3 June 2003/ Returned for modification 18 July 2003/ Accepted 19 September 2003

The activity of the acyclic nucleotide analogue 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine [(S)-HPMPA] against Schistosoma mansoni was investigated in mice. The compound was injected intraperitoneally, usually on two or five consecutive days, at 10 to 20 mg/kg of body weight/day. The treatment started before, at the time of, and after the onset of egg laying (oviposition) by S. mansoni. The animals were killed from 7 to 40 days after the cessation of treatment. Significant reductions in the total numbers of female and coupled worms were found. Female fecundity and both hepatic and intestinal egg loads were suppressed. These effects were more pronounced with dosing regimens launched before the time of oviposition. The complete disappearance of immature eggs and a significant reduction to the complete absence of mature eggs, with 99 to 100% of the eggs being dead, were produced. No hepatic egg-induced granulomas were present in mice treated at the time of oviposition, and the granulomas were smaller in mice treated before S. mansoni oviposition. These preliminary findings extend the knowledge of the antiparasitic properties of (S)-HPMPA.

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