Elucidation of the in vitro and in vivo activities of bridged 1,2,4-trioxolanes, bridged 1,2,4,5-tetraoxanes, tricyclic monoperoxides, silyl peroxides, and hydroxylamine derivatives against Schistosoma mansoni

Bioorganic & Medicinal Chemistry
Noemi CowanJennifer Keiser

Abstract

Praziquantel is currently the only drug available to treat schistosomiasis. Since drug resistance would be a major barrier for the increasing global attempts to eliminate schistosomiasis as a public health problem, efforts should go hand in hand with the discovery of novel treatment options. Synthetic peroxides might offer a good direction since their antischistosomal activity has been demonstrated in the laboratory. We studied 19 bridged 1,2,4,5-tetraoxanes, 2 tricyclic monoperoxides, 11 bridged 1,2,4-trioxolanes, 12 silyl peroxides, and 4 hydroxylamine derivatives against newly transformed schistosomula (NTS) and adult Schistosoma mansoni in vitro. Schistosomicidal compounds were tested for cytotoxicity followed by in vivo studies of the most promising compounds. Tricyclic monoperoxides, trioxolanes, and tetraoxanes revealed the highest in vitro activity against NTS (IC50s 0.4-20.2 μM) and adult schistosomes (IC50s 1.8-22.8 μM). Tetraoxanes showed higher cytotoxicity than antischistosomal activity. Selected trioxolane and tricyclic monoperoxides were tested in mice harboring an adult S. mansoni infection. The highest activity was observed for two trioxolanes, which showed moderate worm burden reductions (WBR) of 44.3% and 42....Continue Reading

References

Jan 4, 2003·Chembiochem : a European Journal of Chemical Biology·Norma R Sperandeo, Reto Brun
Nov 22, 2005·Expert Opinion on Drug Delivery·Thorsteinn LoftssonTomi Järvinen
Dec 16, 2005·AAPS PharmSciTech·Rajeswari ChallaR K Khar
Feb 9, 2011·Antimicrobial Agents and Chemotherapy·Vincent PradinesAnne Robert
Nov 23, 2011·Antimicrobial Agents and Chemotherapy·Jennifer KeiserJonathan L Vennerstrom
Apr 4, 2012·Antimicrobial Agents and Chemotherapy·Katrin IngramJennifer Keiser
Oct 17, 2013·Expert Review of Anti-infective Therapy·Stefanie KnoppJürg Utzinger
Aug 12, 2014·The Lancet Global Health·Belen PedriqueJean-Hervé Bradol
Dec 18, 2014·International Journal for Parasitology. Drugs and Drug Resistance·Gordana PanicJennifer Keiser

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Citations

Mar 30, 2017·Infectious Diseases of Poverty·Robert BergquistJennifer Keiser
Apr 6, 2017·Revista Do Instituto De Medicina Tropical De São Paulo·Thiago José Matos-RochaMaira Galdino da Rocha Pitta
Dec 22, 2016·Revista Da Sociedade Brasileira De Medicina Tropical·Ehssan Ahmed HassanMaha Farid Mohamed Soliman
Nov 4, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vera A Vil'Alexander O Terent'ev
Dec 14, 2017·Future Medicinal Chemistry·Eloi M LagoJosué de Moraes
Jun 22, 2016·Antimicrobial Agents and Chemotherapy·M O Faruk KhanTimothy J Hubin
Feb 14, 2019·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Dmitri V KazakovAlexander O Terent'ev
Jan 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Lília I L CabralMaria L S Cristiano
Apr 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ivan A YaremenkoAlexander O Terent'ev
Jan 13, 2021·ACS Infectious Diseases·Kimberley M ZornConor R Caffrey
Sep 7, 2019·Journal of Natural Products·Oxana B KazakovaKyrill Yu Suponitsky

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