Activity of9-(S)-[3-Hydroxy-2-(Phosphonomethoxy)Propyl]AdenineagainstSchistosomiasis mansoniinMice

Abstract

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.

Cidofovir and (S)-9-[3-Hydroxy-(2-Phosphonomethoxy)Propyl]Adenine Are Highly Effective Inhibitors of Vaccinia Virus DNA Polymerase When Incorporated into the Template Strand

“…Although the drug did not show any activity against human immunodeficiency virus in its original formulation (30), Hostetler et al have recently shown that the alkoxyalkyl ester derivatives are active against this virus, as well as against mutant viruses resistant to azidothymidine, lamivudine, tenofovir, and nevirapine (14). The antimicrobial range of (S)-HPMPA also includes parasites such as trypanosomes (17,18), Schistosoma mansoni (7), and Plasmodium falciparum and Plasmodium berghei (13,34).…”

Antischistosomal Activity of Hexadecyloxypropyl Cyclic 9-( S )-[3-Hydroxy-2-(Phosphonomethoxy)Propyl]Adenine and Other Alkoxyalkyl Esters of Acyclic Nucleoside Phosphonates Assessed by Schistosome Worm Killing In Vitro

“…We previously reported antischistosomal activity for (S)-HPMPA (4), as it caused significant reductions in vivo in worm loads, tissue egg loads, and the frequency of egg developmental stages. Most prominently, (S)-HPMPA treatment resulted in the nearly complete disappearance of mature and immature eggs (4). In vitro, (S)-HPMPA did not significantly affect the muscle tension of S. mansoni worms regardless of the concentration tested (4).…”

“…Most prominently, (S)-HPMPA treatment resulted in the nearly complete disappearance of mature and immature eggs (4). In vitro, (S)-HPMPA did not significantly affect the muscle tension of S. mansoni worms regardless of the concentration tested (4). In this report we have evaluated the antischistosomal activity of various alkoxyalkyl esters of (S)-HPMPA, CDV, and other acyclic nucleoside phosphonate compounds to assess their potential antischistosomal activities.…”

“…It would be of interest to examine the in vivo effects of these compounds in S. mansoni-infected animals, because a previous study with (S)-HPMPA found promising in vivo activity (4). …”

In Vitro Antischistosomal Activity and Cytotoxicity of 5-Methoxylated Flavones fom Vochysia divergens, a Flood-Adapted Species from Brazilian Pantanal

“…Low cure rates and treatment failure following praziquantel administration together with the existence of resistant strains reinforces the need to develop new safe and effective schistosomicidal agents [8,9]. As part of our advancing investigation on the schistosomicidal activity of Brazilian species from "Cerrado" and "Pantanal" [10][11][12], the present work reports on the in vitro schistosomicidal activity of the ethanolic extract and three isolated 5-methoxy-flavones from V. divergens leaves.…”