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
References
Aug 15, 2002·Transactions of the Royal Society of Tropical Medicine and Hygiene·Jürg UtzingerMarcel Tanner
Jun 23, 2006·The Lancet Infectious Diseases·Peter SteinmannJürg Utzinger
Sep 26, 2006·Lancet·Bruno GryseelsLuc Kestens
Feb 7, 2007·Antimicrobial Agents and Chemotherapy·Shu-Hua XiaoMarcel Tanner
Oct 24, 2007·Journal of Medicinal Chemistry·Xiaofang WangJonathan L Vennerstrom
Nov 3, 2007·Current Opinion in Infectious Diseases·Jennifer Keiser, Jürg Utzinger
Apr 19, 2008·Epidemiology and Infection·A J HallL E Haddy
Jul 15, 2009·Antimicrobial Agents and Chemotherapy·Jérôme BoissierBernard Meunier
Jul 21, 2009·Bioorganic & Medicinal Chemistry Letters·Xiaofang WangJonathan L Vennerstrom
Aug 25, 2009·Bioorganic & Medicinal Chemistry Letters·Derek C MartynJon Clardy
Aug 25, 2009·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Katherine A de Villiers, Timothy J Egan
Oct 10, 2009·Parasitology·T ManneckJ Keiser
Dec 8, 2009·Parasitology·J Keiser
Mar 26, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paul M O'NeillStephen A Ward
Mar 31, 2010·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jennifer KeiserEliézer K N'Goran
Apr 29, 2010·Journal of Medicinal Chemistry·Qingjie ZhaoJonathan L Vennerstrom
Aug 25, 2010·Experimental Parasitology·Theresia ManneckJennifer Keiser
Jan 29, 2011·Journal of Clinical Microbiology·Theresia ManneckJennifer Keiser
May 24, 2011·The Journal of Antimicrobial Chemotherapy·Jennifer KeiserMireille Vargas
Jun 1, 2011·Parasitology Research·Hong-Jun LiYou-Sheng Liang
Jun 15, 2011·ACS Medicinal Chemistry Letters·Charles E SchiaffoPatrick H Dussault
Nov 23, 2011·Antimicrobial Agents and Chemotherapy·Jennifer KeiserJonathan L Vennerstrom
Dec 28, 2011·Parasitology Research·Shu-Hua XiaoPei-Ying Jiao
Apr 4, 2012·Antimicrobial Agents and Chemotherapy·Katrin IngramJennifer Keiser
Oct 1, 2007·Expert Opinion on Drug Discovery·Bernadette RamirezSolomon Nwaka
Citations
Aug 15, 2013·Parasites & Vectors·Gordana PanicJennifer Keiser
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
Dec 23, 2014·Acta Tropica·Shereen F MossallamMarwa H El-Faham
Nov 4, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vera A Vil'Alexander O Terent'ev
Oct 5, 2016·Antimicrobial Agents and Chemotherapy·Anna LeonidovaJennifer Keiser
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
Sep 12, 2019·Current Topics in Medicinal Chemistry·Vera A Vil'Olga M Mulina
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
Oct 30, 2020·Infection and Drug Resistance·Amany Ibrahim AmmarAmany Ahmed Rady
Jun 18, 2021·Frontiers in Immunology·José T Moreira-FilhoCarolina H Andrade
Jul 12, 2014·Chemical Reviews·Mathew NjorogeKelly Chibale