In vitro and in vivo activity of 3-alkoxy-1,2-dioxolanes against Schistosoma mansoni.

The Journal of Antimicrobial Chemotherapy
Katrin IngramJennifer Keiser

Abstract

Compounds characterized by a peroxidic skeleton are an interesting starting point for antischistosomal drug discovery. Previously a series of 3-alkoxy-1,2-dioxolanes, which are chemically stable cyclic peroxides, demonstrated significant in vitro activity against Plasmodium falciparum. We aimed to evaluate the potential of these compounds against Schistosoma mansoni and elucidate the roles of iron and peroxidic groups in activity. Drugs were tested against juvenile and adult stages of S. mansoni in vitro and in vivo. Selected structures were assessed in vitro against schistosomes in the presence of additional iron sources. In addition, drugs were tested in vitro and in vivo against Echinostoma caproni, a non-blood-feeding intestinal fluke. Finally, the activity of non-peroxidic analogues was evaluated. Three dioxolanes displayed IC₅₀s ≤ 20.1 μM against adult schistosomes and values as low as 4.2 μM against newly transformed schistosomula. Nonetheless, only moderate, non-significant worm burden reductions were observed after treatment of mice harbouring adult infections. Drugs lacked activity against juvenile schistosomes in vivo. Two selected dioxolanes showed in vitro activity against E. caproni down to concentrations of 5 mg/...Continue Reading

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Citations

Dec 18, 2014·International Journal for Parasitology. Drugs and Drug Resistance·Gordana PanicJennifer Keiser
Jan 8, 2016·Transactions of the Royal Society of Tropical Medicine and Hygiene·R Toledo, J G Esteban
Nov 4, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vera A Vil'Alexander O Terent'ev
Jul 2, 2014·Antimicrobial Agents and Chemotherapy·Isabel MeisterJennifer Keiser
Oct 3, 2018·Chemistry & Biodiversity·Vinícius R D PereiraAdemar A Da Silva Filho
Jan 29, 2019·PLoS Neglected Tropical Diseases·Sören FrahmClarissa Prazeres da Costa
Aug 26, 2016·Beilstein Journal of Organic Chemistry·Ivan A YaremenkoAlexander O Terent'ev
Jan 24, 2014·Beilstein Journal of Organic Chemistry·Alexander O Terent'evValery M Dembitsky
Aug 16, 2013·Beilstein Journal of Organic Chemistry·Wantanee SittiwongPatrick H Dussault
Jun 18, 2021·Frontiers in Immunology·José T Moreira-FilhoCarolina H Andrade

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