Bioactive Natural and Synthetic Peroxides for the Treatment of Helminth and Protozoan Pathogens: Synthesis and Properties

Hotez, P.J.; Brindley, P.J.; Bethony, J.M.; King, C.H.; Pearce, E.J.; Jacobson, J. Helminth infections: The great neglected tropical diseases. J. Clin. Invest., 2008, 118(4), 1311-1321.
[http://dx.doi.org/10.1172/JCI34261] [PMID: 18382743]

Gilles, H.M.; Hoffman, P.S. Treatment of intestinal parasitic infections: A review of nitazoxanide. Trends Parasitol., 2002, 18(3), 95-97.
[http://dx.doi.org/10.1016/S1471-4922(01)02205-X] [PMID: 11854075]

Conteh, L.; Engels, T.; Molyneux, D.H. Socioeconomic aspects of neglected tropical diseases. Lancet, 2010, 375(9710), 239-247.
[http://dx.doi.org/10.1016/S0140-6736(09)61422-7] [PMID: 20109925]

Hotez, P.J.; Damania, A. India’s neglected tropical diseases. PLoS Negl. Trop. Dis., 2018, 12(3)e0006038
[http://dx.doi.org/10.1371/journal.pntd.0006038] [PMID: 29565970]

World Health Organization. Investing to overcome the global impact of neglected tropical diseases, 2015.

Geary, T.G. Are new anthelmintics needed to eliminate human helminthiases? Curr. Opin. Infect. Dis., 2012, 25(6), 709-717.
[http://dx.doi.org/10.1097/QCO.0b013e328359f04a] [PMID: 23041774]

Patnaik, P. In A Comprehensive Guide to the Hazardous Properties of Chemical Substances; John Wiley & Sons, Inc., 2006, pp. 719-740.
[http://dx.doi.org/10.1002/9780470134955.ch43]

Liebman, J.F.; Greer, A., Eds.; The Chemistry of Peroxides; John Wiley & Sons: New York, 2006.

Klapötke, T.M. Wloka, T.PATAI’S Chemistry of Functional Groups; John Wiley & Sons, Ltd, 2009.

Denisov, E.T.; Denisova, T.G.; Pokidova, T.S. In Handbook of Free Radical Initiators; John Wiley & Sons, Inc., 2005, pp. 129-282.
[http://dx.doi.org/10.1002/0471721476.ch5]

Gaylord, N.G.; Mandal, B.M.; Martan, M. Peroxide-induced polymerization of norbornene. J. Polym. Sci. Polym. Lett. Ed., 1976, 14(9), 555-559.
[http://dx.doi.org/10.1002/pol.1976.130140908]

Emami, S.H.; Salovey, R.; Hogen-Esch, T.E. Peroxide-mediated crosslinking of poly(ethylene oxide). J. Polym. Sci. A Polym. Chem., 2002, 40(17), 3021-3026.
[http://dx.doi.org/10.1002/pola.10367]

Russell, K.E. Free radical graft polymerization and copolymerization at higher temperatures. Prog. Polym. Sci., 2002, 27(6), 1007-1038.
[http://dx.doi.org/10.1016/S0079-6700(02)00007-2]

Adam, W., Ed.; Peroxide Chemistry: Mechanistic and Preparative Aspects of Oxygen Transfer; Wiley-VCH Verlag GmbH & Co: KGaA, Weinheim, FRG. , 2005, pp. 494-510.
[http://dx.doi.org/10.1002/3527600396.ch23]

Mishra, M.; Yagci, Y., Eds.; Handbook of Vinyl Polymers: Radical Polymerization, Process, and Technology, 2ND Ed.; CRC Press, Taylor & Francis Group, 2008.

Ukuku, D.O. Decontamination of Fresh and Minimally Processed Produce; Wiley-Blackwell: New Jersey, USA, 2012, pp. 197-214.
[http://dx.doi.org/10.1002/9781118229187]

Kitis, M. Disinfection of wastewater with peracetic acid: A review. Environ. Int., 2004, 30(1), 47-55.
[http://dx.doi.org/10.1016/S0160-4120(03)00147-8] [PMID: 14664864]

Chassot, A.L.C.; Poisl, M.I.P.; Samuel, S.M.W. In vivo and in vitro evaluation of the efficacy of a peracetic acid-based disinfectant for decontamination of acrylic resins. Braz. Dent. J., 2006, 17(2), 117-121.
[http://dx.doi.org/10.1590/S0103-64402006000200006] [PMID: 16924337]

Baldry, M.G.C.; French, M.S. Disinfection of sewage effluent with peracetic acid. Water Sci. Technol., 1989, 21(3), 203-206.
[http://dx.doi.org/10.2166/wst.1989.0100]

Alvaro, J.E.; Moreno, S.; Dianez, F.; Santos, M.; Carrasco, G.; Urrestarazu, M. Effects of peracetic acid disinfectant on the postharvest of some fresh vegetables. J. Food Eng., 2009, 95(1), 11-15.
[http://dx.doi.org/10.1016/j.jfoodeng.2009.05.003]

McDonnell, G. In PATAI’S Chemistry of Functional Groups; John Wiley & Sons, Ltd: New York, 2009.

Omidbakhsh, N. A new peroxide-based flexible endoscope-compatible high-level disinfectant. Am. J. Infect. Control, 2006, 34(9), 571-577.
[http://dx.doi.org/10.1016/j.ajic.2006.02.003] [PMID: 17097451]

Luukkonen, T.; Pehkonen, S.O. Peracids in water treatment: A critical review. Crit. Rev. Environ. Sci. Technol., 2017, 47(1), 1-39.
[http://dx.doi.org/10.1080/10643389.2016.1272343]

Mao, W. Zhang, Y.; Zhang, A. Case Studies in Modern Drug Discovery and Development; John Wiley & Sons, Inc.: New York, 2012, pp. 227-256.
[http://dx.doi.org/10.1002/9781118219683.ch10]

Tu, Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat. Med., 2011, 17(10), 1217-1220.
[http://dx.doi.org/10.1038/nm.2471] [PMID: 21989013]

White, N.J.; Hien, T.T.; Nosten, F.H. A brief history of Qinghaosu. Trends Parasitol., 2015, 31(12), 607-610.
[http://dx.doi.org/10.1016/j.pt.2015.10.010] [PMID: 26776328]

Xu, T.; Feng, Q.; Jacob, M.R.; Avula, B.; Mask, M.M.; Baerson, S.R.; Tripathi, S.K.; Mohammed, R.; Hamann, M.T.; Khan, I.A.; Walker, L.A.; Clark, A.M.; Agarwal, A.K. The marine sponge-derived polyketide endoperoxide plakortide F acid mediates its antifungal activity by interfering with calcium homeostasis. Antimicrob. Agents Chemother., 2011, 55(4), 1611-1621.
[http://dx.doi.org/10.1128/AAC.01022-10] [PMID: 21300833]

Tu, Y.Y.; Ni, M.Y.; Zhong, Y.R.; Li, L.N.; Cui, S.L.; Zhang, M.Q.; Wang, X.Z.; Liang, X.T. Studies on the constituents of Artemisia annua L. (author’s transl). Yao Xue Xue Bao, 1981, 16(5), 366-370.
[PMID: 7246183]

Miller, L.H.; Su, X. Artemisinin: Discovery from the Chinese herbal garden. Cell, 2011, 146(6), 855-858.
[http://dx.doi.org/10.1016/j.cell.2011.08.024] [PMID: 21907397]

Robert, A.; Dechy-Cabaret, O.; Cazelles, J.; Meunier, B. From mechanistic studies on artemisinin derivatives to new modular antimalarial drugs. Acc. Chem. Res., 2002, 35(3), 167-174.
[http://dx.doi.org/10.1021/ar990164o] [PMID: 11900520]

Gelb, M.H. Drug discovery for malaria: A very challenging and timely endeavor. Curr. Opin. Chem. Biol., 2007, 11(4), 440-445.
[http://dx.doi.org/10.1016/j.cbpa.2007.05.038] [PMID: 17761335]

Capela, R.; Oliveira, R.; Gonçalves, L.M.; Domingos, A.; Gut, J.; Rosenthal, P.J.; Lopes, F.; Moreira, R. Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition. Bioorg. Med. Chem. Lett., 2009, 19(12), 3229-3232.
[http://dx.doi.org/10.1016/j.bmcl.2009.04.100] [PMID: 19435664]

Jones, M.; Mercer, A.E.; Stocks, P.A.; La Pensée, L.J.; Cosstick, R.; Park, B.K.; Kennedy, M.E.; Piantanida, I.; Ward, S.A.; Davies, J.; Bray, P.G.; Rawe, S.L.; Baird, J.; Charidza, T.; Janneh, O.; O’Neill, P.M. Antitumour and antimalarial activity of artemisinin-acridine hybrids. Bioorg. Med. Chem. Lett., 2009, 19(7), 2033-2037.
[http://dx.doi.org/10.1016/j.bmcl.2009.02.028] [PMID: 19249201]

White, N.J. Qinghaosu (artemisinin): The price of success. Science, 2008, 320(5874), 330-334.
[http://dx.doi.org/10.1126/science.1155165] [PMID: 18420924]

Shah, F.; Zhang, S-Q.; Kandhari, S.P.; Mukherjee, P.; Chittiboyina, A.; Avery, M.A.; Avery, B.A. In vitro erythrocytic uptake studies of artemisinin and selected derivatives using LC-MS and 2D-QSAR analysis of uptake in parasitized erythrocytes. Bioorg. Med. Chem., 2009, 17(14), 5325-5331.
[http://dx.doi.org/10.1016/j.bmc.2009.05.026] [PMID: 19497754]

Mäser, P.; Wittlin, S.; Rottmann, M.; Wenzler, T.; Kaiser, M.; Brun, R. Antiparasitic agents: New drugs on the horizon. Curr. Opin. Pharmacol., 2012, 12(5), 562-566.
[http://dx.doi.org/10.1016/j.coph.2012.05.001] [PMID: 22652215]

Ruiz, J.; Tuccio, B.; Lauricella, R.; Maynadier, M.; Vial, H.; André-Barrès, C. Synthesis and antiplasmodial evaluation of cyclopropyl analogs of the G-factor bicyclic peroxide. Tetrahedron, 2013, 69(32), 6709-6720.
[http://dx.doi.org/10.1016/j.tet.2013.05.099]

Ruiz, J.; Mallet-Ladeira, S.; Maynadier, M.; Vial, H.; André-Barrès, C. Design, synthesis and evaluation of new tricyclic endoperoxides as potential antiplasmodial agents. Org. Biomol. Chem., 2014, 12(28), 5212-5221.
[http://dx.doi.org/10.1039/C4OB00787E] [PMID: 24914508]

Ruiz, J.; Azema, J.; Payrastre, C.; Baltas, M.; Tuccio, B.; Vial, H.; Andre-Barres, C. Antimalarial bicyclic peroxides belonging to the G-factor family: Mechanistic aspects of their formation and iron (II) induced reduction. Curr. Top. Med. Chem., 2014, 14(14), 1668-1683.
[http://dx.doi.org/10.2174/1568026614666140808154326] [PMID: 25116578]

Ann Casteel, D. Peroxy natural products. Nat. Prod. Rep., 1999, 16(1), 55-73.
[http://dx.doi.org/10.1039/a705725c]

Liang, X.T.; Yu, D.Q.; Wu, W.L.; Deng, H.C. The structure of Yingzhaosu A. Acta Chimi. Sin., 1979, 37, 215-230.

Jakupovic, J.; Grenz, M.; Schmeda-Hirschmann, G. Rhamnofolane derivatives from Jatropha grossidentata. Phytochemistry, 1988, 27(9), 2997-2998.
[http://dx.doi.org/10.1016/0031-9422(88)80710-6]

Bohlmann, F.; Abraham, W-R. Neue diterpene aus Helichrysum acutatum. Phytochemistry, 1979, 18(10), 1754-1756.
[http://dx.doi.org/10.1016/0031-9422(79)80208-3]

Itokawa, H.; Takega, K. Antitumor substtances from higher plants. Yakugaku Zasshi, 1993, 119(8), 529-583.
[PMID: 10475056]

Tang, Y.; Dong, Y.; Vennerstrom, J.L. Synthetic peroxides as antimalarials. Med. Res. Rev., 2004, 24(4), 425-448.
[http://dx.doi.org/10.1002/med.10066] [PMID: 15170591]

Vennerstrom, J.L.; Arbe-Barnes, S.; Brun, R.; Charman, S.A.; Chiu, F.C.K.; Chollet, J.; Dong, Y.; Dorn, A.; Hunziker, D.; Matile, H.; McIntosh, K.; Padmanilayam, M.; Santo Tomas, J.; Scheurer, C.; Scorneaux, B.; Tang, Y.; Urwyler, H.; Wittlin, S.; Charman, W.N. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature, 2004, 430(7002), 900-904.
[http://dx.doi.org/10.1038/nature02779] [PMID: 15318224]

Dong, Y.; Wittlin, S.; Sriraghavan, K.; Chollet, J.; Charman, S.A.; Charman, W.N.; Scheurer, C.; Urwyler, H.; Santo Tomas, J.; Snyder, C.; Creek, D.J.; Morizzi, J.; Koltun, M.; Matile, H.; Wang, X.; Padmanilayam, M.; Tang, Y.; Dorn, A.; Brun, R.; Vennerstrom, J.L. The structure-activity relationship of the antimalarial ozonide arterolane (OZ277). J. Med. Chem., 2010, 53(1), 481-491.
[http://dx.doi.org/10.1021/jm901473s] [PMID: 19924861]

Rathi, A. Ranbaxy launches new anti-malarial Synriam. Chemistry World, 2012, 3, 2012.

Dong, Y.; Wang, X.; Kamaraj, S.; Bulbule, V.J.; Chiu, F.C.K.; Chollet, J.; Dhanasekaran, M.; Hein, C.D.; Papastogiannidis, P.; Morizzi, J.; Shackleford, D.M.; Barker, H.; Ryan, E.; Scheurer, C.; Tang, Y.; Zhao, Q.; Zhou, L.; White, K.L.; Urwyler, H.; Charman, W.N.; Matile, H.; Wittlin, S.; Charman, S.A.; Vennerstrom, J.L. Structure–activity relationship of the antimalarial ozonide Artefenomel (OZ439). J. Med. Chem., 2017, 60(7), 2654-2668.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01586] [PMID: 28052200]

Kim, H.S.; Hammill, J.T.; Guy, R.K. Seeking the elusive long-acting ozonide: discovery of Artefenomel (OZ439). J. Med. Chem., 2017, 60(7), 2651-2653.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00299] [PMID: 28296396]

Dembitsky, V.M. Bioactive peroxides as potential therapeutic agents. Eur. J. Med. Chem., 2008, 43(2), 223-251.
[http://dx.doi.org/10.1016/j.ejmech.2007.04.019] [PMID: 17618015]

Ibrahim, S.R.M.; Ebel, R.; Wray, V.; Müller, W.E.G.; Edrada-Ebel, R.; Proksch, P. Diacarperoxides, norterpene cyclic peroxides from the sponge Diacarnus megaspinorhabdosa. J. Nat. Prod., 2008, 71(8), 1358-1364.
[http://dx.doi.org/10.1021/np800102u] [PMID: 18672931]

Liu, D-Z.; Liu, J-K. Peroxy natural products. Nat. Prod. Bioprospect., 2013, 3(5), 161-206.
[http://dx.doi.org/10.1007/s13659-013-0042-7]

Li, H.; Huang, H.; Shao, C.; Huang, H.; Jiang, J.; Zhu, X.; Liu, Y.; Liu, L.; Lu, Y.; Li, M.; Lin, Y.; She, Z. Cytotoxic norsesquiterpene peroxides from the endophytic fungus Talaromyces flavus isolated from the mangrove plant Sonneratia apetala. J. Nat. Prod., 2011, 74(5), 1230-1235.
[http://dx.doi.org/10.1021/np200164k] [PMID: 21545109]

Abrams, R.P.; Carroll, W.L.; Woerpel, K.A. Five-membered ring peroxide selectively initiates ferroptosis in cancer cells. ACS Chem. Biol., 2016, 11(5), 1305-1312.
[http://dx.doi.org/10.1021/acschembio.5b00900] [PMID: 26797166]

Meshnick, S.R.; Jefford, C.W.; Posner, G.H.; Avery, M.A.; Peters, W. Second-generation antimalarial endoperoxides.Parasitol. Today(Regul. Ed.); , 1996, 12, pp. (2)79-82.
[http://dx.doi.org/10.1016/0169-4758(96)80660-0] [PMID: 15275260]

Ploypradith, P. Development of artemisinin and its structurally simplified trioxane derivatives as antimalarial drugs. Acta Trop., 2004, 89(3), 329-342.
[http://dx.doi.org/10.1016/j.actatropica.2003.10.006] [PMID: 14744559]

Jefford, C.W. New developments in synthetic peroxidic drugs as artemisinin mimics. Drug Discov. Today, 2007, 12(11-12), 487-495.
[http://dx.doi.org/10.1016/j.drudis.2007.04.009] [PMID: 17532534]

Opsenica, D.M.; Šolaja, B.A. Antimalarial peroxides. J. Serb. Chem. Soc., 2009, 74(11), 1155-1193.
[http://dx.doi.org/10.2298/JSC0911155O]

Dembitsky, V.M.; Gloriozova, T.A.; Poroikov, V.V. Natural peroxy anticancer agents. Mini Rev. Med. Chem., 2007, 7(6), 571-589.
[http://dx.doi.org/10.2174/138955707780859396] [PMID: 17584156]

Jung, M.; Kim, H.; Lee, K.; Park, M. Naturally occurring peroxides with biological activities. Mini Rev. Med. Chem., 2003, 3(2), 159-165.
[http://dx.doi.org/10.2174/1389557033405313] [PMID: 12570849]

Chaturvedi, D.; Goswami, A.; Saikia, P.P.; Barua, N.C.; Rao, P.G. Artemisinin and its derivatives: A novel class of anti-malarial and anti-cancer agents. Chem. Soc. Rev., 2010, 39(2), 435-454.
[http://dx.doi.org/10.1039/B816679J] [PMID: 20111769]

Lee, S. Artemisinin, promising lead natural product for various drug developments. Mini Rev. Med. Chem., 2007, 7(4), 411-422.
[http://dx.doi.org/10.2174/138955707780363837] [PMID: 17430226]

Pandey, N.; Pandey-Rai, S. Updates on artemisinin: An insight to mode of actions and strategies for enhanced global production. Protoplasma, 2016, 253(1), 15-30.
[http://dx.doi.org/10.1007/s00709-015-0805-6] [PMID: 25813833]

Yao, W.; Wang, F.; Wang, H. Immunomodulation of artemisinin and its derivatives. Sci. Bull. (Beijing), 2016, 61(18), 1399-1406.
[http://dx.doi.org/10.1007/s11434-016-1105-z]

Utzinger, J.; Xiao, S.; N’Goran, E.K.; Bergquist, R.; Tanner, M. The potential of artemether for the control of schistosomiasis. Int. J. Parasitol., 2001, 31(14), 1549-1562.
[http://dx.doi.org/10.1016/S0020-7519(01)00297-1] [PMID: 11730781]

Utzinger, J.; Xiao, S.; Keiser, J.; Chen, M.; Zheng, J.; Tanner, M. Current progress in the development and use of artemether for chemoprophylaxis of major human schistosome parasites. Curr. Med. Chem., 2001, 8(15), 1841-1860.
[http://dx.doi.org/10.2174/0929867013371581] [PMID: 11772354]

Keiser, J.; Utzinger, J. Food-borne trematodiasis: Current chemotherapy and advances with artemisinins and synthetic trioxolanes. Trends Parasitol., 2007, 23(11), 555-562.
[http://dx.doi.org/10.1016/j.pt.2007.07.012] [PMID: 17950667]

Muraleedharan, K.M.; Avery, M.A. Progress in the development of peroxide-based anti-parasitic agents. Drug Discov. Today, 2009, 14(15-16), 793-803.
[http://dx.doi.org/10.1016/j.drudis.2009.05.008] [PMID: 19477287]

Panic, G.; Duthaler, U.; Speich, B.; Keiser, J. Repurposing drugs for the treatment and control of helminth infections. Int. J. Parasitol. Drugs Drug Resist., 2014, 4(3), 185-200.
[http://dx.doi.org/10.1016/j.ijpddr.2014.07.002] [PMID: 25516827]

Lago, E.M.; Xavier, R.P.; Teixeira, T.R.; Silva, L.M.; da Silva Filho, A.A.; de Moraes, J. Antischistosomal agents: State of art and perspectives. Future Med. Chem., 2018, 10(1), 89-120.
[http://dx.doi.org/10.4155/fmc-2017-0112] [PMID: 29235368]

Panic, G.; Keiser, J. Acting beyond 2020: Better characterization of praziquantel and promising antischistosomal leads. Curr. Opin. Pharmacol., 2018, 42, 27-33.
[http://dx.doi.org/10.1016/j.coph.2018.06.004] [PMID: 30077117]

Vacher, M. Fdez. Galván, I.; Ding, B.-W.; Schramm, S.; Berraud-Pache, R.; Naumov, P.; Ferré, N.; Liu, Y.-J.; Navizet, I.; Roca-Sanjuán, D.; Baader, W.J.; Lindh, R. Chemi- and bioluminescence of cyclic peroxides. Chem. Rev., 2018, 118(15), 6927-6974.
[http://dx.doi.org/10.1021/acs.chemrev.7b00649]

Ananikov, V.P.; Eremin, D.B.; Yakukhnov, S.A.; Dilman, A.D.; Levin, V.V.; Egorov, M.P.; Karlov, S.S.; Kustov, L.M.; Tarasov, A.L.; Greish, A.A.; Shesterkina, A.A.; Sakharov, A.M.; Nysenko, Z.N.; Sheremetev, A.B.; Stakheev, A.Y.; Mashkovsky, I.S.; Sukhorukov, A.Y.; Ioffe, S.L.; Terent’ev, A.O.; Vil’, V.A.; Tomilov, Y.V.; Novikov, R.A.; Zlotin, S.G.; Kucherenko, A.S.; Ustyuzhanina, N.E.; Krylov, V.B.; Tsvetkov, Y.E.; Gening, M.L.; Nifantiev, N.E. Organic and hybrid systems: from science to practice. Mendeleev Commun., 2017, 27(5), 425-438.
[http://dx.doi.org/10.1016/j.mencom.2017.09.001]

Lu, X.; Liu, Y.; Sun, B.; Cindric, B.; Deng, L. Catalytic enantioselective peroxidation of α,β-unsaturated ketones. J. Am. Chem. Soc., 2008, 130(26), 8134-8135.
[http://dx.doi.org/10.1021/ja802982h] [PMID: 18529055]

Schiaffo, C.E.; Rottman, M.; Wittlin, S.; Dussault, P.H. 3-Alkoxy-1,2-dioxolanes: Synthesis and evaluation as potential antimalarial agents. ACS Med. Chem. Lett., 2011, 2(4), 316-319.
[http://dx.doi.org/10.1021/ml100308d] [PMID: 21666827]

Kyasa, S.; Puffer, B.W.; Dussault, P.H. Synthesis of alkyl hydroperoxides via alkylation of gem-dihydroperoxides. J. Org. Chem., 2013, 78(7), 3452-3456.
[http://dx.doi.org/10.1021/jo4001564] [PMID: 23469994]

Gomes, G.D.P.; Vil’, V.; Terent’ev, A.; Alabugin, I.V. Stereoelectronic source of the anomalous stability of bis-peroxides. Chem. Sci. (Camb.), 2015, 6(12), 6783-6791.
[http://dx.doi.org/10.1039/C5SC02402A] [PMID: 28757970]

Starkl Renar, K.; Pečar, S.; Iskra, J. Activation of aqueous hydrogen peroxide for non-catalyzed dihydroperoxidation of ketones by azeotropic removal of water. Org. Biomol. Chem., 2015, 13(36), 9369-9372.
[http://dx.doi.org/10.1039/C5OB01503K] [PMID: 26289229]

Dos Passos Gomes, G.; Yaremenko, I.A.; Radulov, P.S.; Novikov, R.A.; Chernyshev, V.V.; Korlyukov, A.A.; Nikishin, G.I.; Alabugin, I.V.; Terent’ev, A.O. Stereoelectronic control in the ozone‐free synthesis of ozonides. Angew. Chem. Int. Ed. Engl., 2017, 56(18), 4955-4959.
[http://dx.doi.org/10.1002/anie.201610699] [PMID: 28378382]

Terent’ev, A.O.; Platonov, M.M.; Krylov, I.B.; Chernyshev, V.V.; Nikishin, G.I. Synthesis of 1-hydroperoxy-1′-alkoxyperoxides by the iodine-catalyzed reactions of geminal bishydroperoxides with acetals or enol ethers. Org. Biomol. Chem., 2008, 6(23), 4435-4441.
[http://dx.doi.org/10.1039/b809661a] [PMID: 19005604]

Terent’ev, A.O.; Kutkin, A.V.; Troizky, N.A.; Ogibin, Y.N.; Nikishin, G.I. Synthesis of geminal bisperoxides by acid-catalyzed reaction of acetals and enol ethers with tert-butyl hydroperoxide. Synthesis, 2005, 2005(13), 2215-2219.
[http://dx.doi.org/10.1055/s-2005-872093]

Vil’, V.A.; Dos Passos Gomes, G.; Bityukov, O.V.; Lyssenko, K.A.; Nikishin, G.I.; Alabugin, I.V.; Terent’ev, A.O. Interrupted Baeyer–Villiger rearrangement: building a stereoelectronic trap for the Criegee intermediate. Angew. Chem. Int. Ed. Engl., 2018, 57(13), 3372-3376.
[http://dx.doi.org/10.1002/anie.201712651] [PMID: 29385307]

Chen, H-J.; Wu, Y. Expeditious entry to the chamigrane endoperoxide family of natural products. Org. Lett., 2015, 17(3), 592-595.
[http://dx.doi.org/10.1021/ol503603t] [PMID: 25583367]

Hilf, J.A.; Witthoft, L.W.; Woerpel, K.A. An SN1-type reaction to form the 1,2-dioxepane ring: synthesis of 10,12-peroxycalamenene. J. Org. Chem., 2015, 80(16), 8262-8267.
[http://dx.doi.org/10.1021/acs.joc.5b01326] [PMID: 26158427]

Miner, M.R.; Woerpel, K.A. CuI‐Catalyzed synthesis of propargyl hydroperoxides using molecular oxygen and hydroxylamines. Eur. J. Org. Chem., 2016, 2016(10), 1860-1866.
[http://dx.doi.org/10.1002/ejoc.201600038]

Ghogare, A.A.; Greer, A. Using singlet oxygen to synthesize natural products and drugs. Chem. Rev., 2016, 116(17), 9994-10034.
[http://dx.doi.org/10.1021/acs.chemrev.5b00726] [PMID: 27128098]

Fisher, T.J.; Dussault, P.H. Alkene ozonolysis. Tetrahedron, 2017, 73(30), 4233-4258.
[http://dx.doi.org/10.1016/j.tet.2017.03.039]

Terent”ev, A.O.; Kutkin, A.V.; Platonov, M.M.; Vorontsov, I.I.; Antipin, M.Y.; Ogibin, Y.N.; Nikishin, G.I. Synthesis of peroxide compounds by the BF3-catalyzed reaction of acetals and enol ethers with H2O2. Russ. Chem. Bull., 2004, 53(3), 681-687.
[http://dx.doi.org/10.1023/B:RUCB.0000035657.58776.cc]

Han, W-B.; Wu, Y. Facile perhydrolysis of oxetanes catalyzed by molybdenum species. Org. Lett., 2014, 16(21), 5706-5709.
[http://dx.doi.org/10.1021/ol502785u] [PMID: 25317500]

Neubig, R.R.; Spedding, M.; Kenakin, T.; Christopoulos, A. International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. International union of pharmacology committee on receptor nomenclature and drug classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol. Rev., 2003, 55(4), 597-606.
[http://dx.doi.org/10.1124/pr.55.4.4] [PMID: 14657418]

Sebaugh, J.L. Guidelines for accurate EC50/IC50 estimation. Pharm. Stat., 2011, 10(2), 128-134.
[http://dx.doi.org/10.1002/pst.426] [PMID: 22328315]

Hotez, P.J.; Molyneux, D.H.; Fenwick, A.; Ottesen, E.; Ehrlich Sachs, S.; Sachs, J.D. Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Med., 2006, 3(5)e102
[http://dx.doi.org/10.1371/journal.pmed.0030102] [PMID: 16435908]

Murray, C.J.L.; Vos, T.; Lozano, R.; Naghavi, M.; Flaxman, A.D.; Michaud, C.; Ezzati, M.; Shibuya, K.; Salomon, J.A.; Abdalla, S.; Aboyans, V.; Abraham, J.; Ackerman, I.; Aggarwal, R.; Ahn, S.Y.; Ali, M.K.; AlMazroa, M.A.; Alvarado, M.; Anderson, H.R.; Anderson, L.M.; Andrews, K.G.; Atkinson, C.; Baddour, L.M.; Bahalim, A.N.; Barker-Collo, S.; Barrero, L.H.; Bartels, D.H.; Basáñez, M-G.; Baxter, A.; Bell, M.L.; Benjamin, E.J.; Bennett, D.; Bernabé, E.; Bhalla, K.; Bhandari, B.; Bikbov, B.; Abdulhak, A.B.; Birbeck, G.; Black, J.A.; Blencowe, H.; Blore, J.D.; Blyth, F.; Bolliger, I.; Bonaventure, A.; Boufous, S.; Bourne, R.; Boussinesq, M.; Braithwaite, T.; Brayne, C.; Bridgett, L.; Brooker, S.; Brooks, P.; Brugha, T.S.; Bryan-Hancock, C.; Bucello, C.; Buchbinder, R.; Buckle, G.; Budke, C.M.; Burch, M.; Burney, P.; Burstein, R.; Calabria, B.; Campbell, B.; Canter, C.E.; Carabin, H.; Carapetis, J.; Carmona, L.; Cella, C.; Charlson, F.; Chen, H.; Cheng, A.T-A.; Chou, D.; Chugh, S.S.; Coffeng, L.E.; Colan, S.D.; Colquhoun, S.; Colson, K.E.; Condon, J.; Connor, M.D.; Cooper, L.T.; Corriere, M.; Cortinovis, M.; de Vaccaro, K.C.; Couser, W.; Cowie, B.C.; Criqui, M.H.; Cross, M.; Dabhadkar, K.C.; Dahiya, M.; Dahodwala, N.; Damsere-Derry, J.; Danaei, G.; Davis, A.; Leo, D.D.; Degenhardt, L.; Dellavalle, R.; Delossantos, A.; Denenberg, J.; Derrett, S.; Des Jarlais, D.C.; Dharmaratne, S.D.; Dherani, M.; Diaz-Torne, C.; Dolk, H.; Dorsey, E.R.; Driscoll, T.; Duber, H.; Ebel, B.; Edmond, K.; Elbaz, A.; Ali, S.E.; Erskine, H.; Erwin, P.J.; Espindola, P.; Ewoigbokhan, S.E.; Farzadfar, F.; Feigin, V.; Felson, D.T.; Ferrari, A.; Ferri, C.P.; Fèvre, E.M.; Finucane, M.M.; Flaxman, S.; Flood, L.; Foreman, K.; Forouzanfar, M.H.; Fowkes, F.G.R.; Fransen, M.; Freeman, M.K.; Gabbe, B.J.; Gabriel, S.E.; Gakidou, E.; Ganatra, H.A.; Garcia, B.; Gaspari, F.; Gillum, R.F.; Gmel, G.; Gonzalez-Medina, D.; Gosselin, R.; Grainger, R.; Grant, B.; Groeger, J.; Guillemin, F.; Gunnell, D.; Gupta, R.; Haagsma, J.; Hagan, H.; Halasa, Y.A.; Hall, W.; Haring, D.; Haro, J.M.; Harrison, J.E.; Havmoeller, R.; Hay, R.J.; Higashi, H.; Hill, C.; Hoen, B.; Hoffman, H.; Hotez, P.J.; Hoy, D.; Huang, J.J.; Ibeanusi, S.E.; Jacobsen, K.H.; James, S.L.; Jarvis, D.; Jasrasaria, R.; Jayaraman, S.; Johns, N.; Jonas, J.B.; Karthikeyan, G.; Kassebaum, N.; Kawakami, N.; Keren, A.; Khoo, J-P.; King, C.H.; Knowlton, L.M.; Kobusingye, O.; Koranteng, A.; Krishnamurthi, R.; Laden, F.; Lalloo, R.; Laslett, L.L.; Lathlean, T.; Leasher, J.L.; Lee, Y.Y.; Leigh, J.; Levinson, D.; Lim, S.S.; Limb, E.; Lin, J.K.; Lipnick, M.; Lipshultz, S.E.; Liu, W.; Loane, M.; Ohno, S.L.; Lyons, R.; Mabweijano, J.; MacIntyre, M.F.; Malekzadeh, R.; Mallinger, L.; Manivannan, S.; Marcenes, W.; March, L.; Margolis, D.J.; Marks, G.B.; Marks, R.; Matsumori, A.; Matzopoulos, R.; Mayosi, B.M.; McAnulty, J.H.; McDermott, M.M.; McGill, N.; McGrath, J.; Medina-Mora, M.E.; Meltzer, M.; Memish, Z.A.; Mensah, G.A.; Merriman, T.R.; Meyer, A-C.; Miglioli, V.; Miller, M.; Miller, T.R.; Mitchell, P.B.; Mock, C.; Mocumbi, A.O.; Moffitt, T.E.; Mokdad, A.A.; Monasta, L.; Montico, M.; Moradi-Lakeh, M.; Moran, A.; Morawska, L.; Mori, R.; Murdoch, M.E.; Mwaniki, M.K.; Naidoo, K.; Nair, M.N.; Naldi, L.; Narayan, K.M.V.; Nelson, P.K.; Nelson, R.G.; Nevitt, M.C.; Newton, C.R.; Nolte, S.; Norman, P.; Norman, R.; O’Donnell, M.; O’Hanlon, S.; Olives, C.; Omer, S.B.; Ortblad, K.; Osborne, R.; Ozgediz, D.; Page, A.; Pahari, B.; Pandian, J.D.; Rivero, A.P.; Patten, S.B.; Pearce, N.; Padilla, R.P.; Perez-Ruiz, F.; Perico, N.; Pesudovs, K.; Phillips, D.; Phillips, M.R.; Pierce, K.; Pion, S.; Polanczyk, G.V.; Polinder, S.; Pope, C.A., III; Popova, S.; Porrini, E.; Pourmalek, F.; Prince, M.; Pullan, R.L.; Ramaiah, K.D.; Ranganathan, D.; Razavi, H.; Regan, M.; Rehm, J.T.; Rein, D.B.; Remuzzi, G.; Richardson, K.; Rivara, F.P.; Roberts, T.; Robinson, C.; De Leòn, F.R.; Ronfani, L.; Room, R.; Rosenfeld, L.C.; Rushton, L.; Sacco, R.L.; Saha, S.; Sampson, U.; Sanchez-Riera, L.; Sanman, E.; Schwebel, D.C.; Scott, J.G.; Segui-Gomez, M.; Shahraz, S.; Shepard, D.S.; Shin, H.; Shivakoti, R.; Silberberg, D.; Singh, D.; Singh, G.M.; Singh, J.A.; Singleton, J.; Sleet, D.A.; Sliwa, K.; Smith, E.; Smith, J.L.; Stapelberg, N.J.C.; Steer, A.; Steiner, T.; Stolk, W.A.; Stovner, L.J.; Sudfeld, C.; Syed, S.; Tamburlini, G.; Tavakkoli, M.; Taylor, H.R.; Taylor, J.A.; Taylor, W.J.; Thomas, B.; Thomson, W.M.; Thurston, G.D.; Tleyjeh, I.M.; Tonelli, M.; Towbin, J.A.; Truelsen, T.; Tsilimbaris, M.K.; Ubeda, C.; Undurraga, E.A.; van der Werf, M.J.; van Os, J.; Vavilala, M.S.; Venketasubramanian, N.; Wang, M.; Wang, W.; Watt, K.; Weatherall, D.J.; Weinstock, M.A.; Weintraub, R.; Weisskopf, M.G.; Weissman, M.M.; White, R.A.; Whiteford, H.; Wiebe, N.; Wiersma, S.T.; Wilkinson, J.D.; Williams, H.C.; Williams, S.R.M.; Witt, E.; Wolfe, F.; Woolf, A.D.; Wulf, S.; Yeh, P-H.; Zaidi, A.K.M.; Zheng, Z-J.; Zonies, D.; Lopez, A.D. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2013;2010: A systematic analysis for the global burden of disease study. The Lancet, 2010, 380(9859), 2197-2223.

Jacobson, J.; Bush, S. Neglected tropical diseases, neglected communities, and conflict: How do we leave no one behind? Trends Parasitol., 2018, 34(3), 175-177.
[http://dx.doi.org/10.1016/j.pt.2017.10.013] [PMID: 29162404]

Hotez, P.J.; Fenwick, A.; Ray, S.E.; Hay, S.I.; Molyneux, D.H. “Rapid impact” 10 years after: The first “decade” (2006-2016) of integrated neglected tropical disease control. PLoS Negl. Trop. Dis., 2018, 12(5)e0006137
[http://dx.doi.org/10.1371/journal.pntd.0006137] [PMID: 29795551]

Booth, M. Advances in Parasitology; Rollinson, D; Stothard, J.R., Ed.; Academic Press, 2018, Vol. 100, pp. 39-126.

Colley, D.G.; Bustinduy, A.L.; Secor, W.E.; King, C.H. Human schistosomiasis. Lancet, 2014, 383(9936), 2253-2264.
[http://dx.doi.org/10.1016/S0140-6736(13)61949-2] [PMID: 24698483]

Gryseels, B.; Polman, K.; Clerinx, J.; Kestens, L. Human schistosomiasis. Lancet, 2006, 368(9541), 1106-1118.
[http://dx.doi.org/10.1016/S0140-6736(06)69440-3] [PMID: 16997665]

Cioli, D.; Pica-Mattoccia, L.; Basso, A.; Guidi, A. Schistosomiasis control: praziquantel forever? Mol. Biochem. Parasitol., 2014, 195(1), 23-29.
[http://dx.doi.org/10.1016/j.molbiopara.2014.06.002] [PMID: 24955523]

Mas-Coma, S.; Bargues, M.D.; Valero, M.A. Fascioliasis and other plant-borne trematode zoonoses. Int. J. Parasitol., 2005, 35(11-12), 1255-1278.
[http://dx.doi.org/10.1016/j.ijpara.2005.07.010] [PMID: 16150452]

Overend, D.J.; Bowen, F.L. Resistance of Fasciola hepatica to triclabendazole. Aust. Vet. J., 1995, 72(7), 275-276.
[http://dx.doi.org/10.1111/j.1751-0813.1995.tb03546.x] [PMID: 8534235]

Coles, G.C.; Rhodes, A.C.; Stafford, K.A. Activity of closantel against adult triclabendazole-resistant Fasciola hepatica. Vet. Rec., 2000, 146(17), 504.
[http://dx.doi.org/10.1136/vr.146.17.504-a] [PMID: 10888001]

Gordon, D.; Zadoks, R.; Skuce, P.; Sargison, N. Confirmation of triclabendazole resistance in liver fluke in the UK. Vet. Rec., 2012, 171(6), 159-160.
[http://dx.doi.org/10.1136/vr.e5381] [PMID: 22890401]

Ortiz, P.; Scarcella, S.; Cerna, C.; Rosales, C.; Cabrera, M.; Guzmán, M.; Lamenza, P.; Solana, H. Resistance of Fasciola hepatica against Triclabendazole in cattle in Cajamarca (Peru): a clinical trial and an in vivo efficacy test in sheep. Vet. Parasitol., 2013, 195(1-2), 118-121.
[http://dx.doi.org/10.1016/j.vetpar.2013.01.001] [PMID: 23352107]

Brockwell, Y.M.; Elliott, T.P.; Anderson, G.R.; Stanton, R.; Spithill, T.W.; Sangster, N.C. Confirmation of Fasciola hepatica resistant to triclabendazole in naturally infected Australian beef and dairy cattle. Int. J. Parasitol. Drugs Drug Resist., 2013, 4(1), 48-54.
[http://dx.doi.org/10.1016/j.ijpddr.2013.11.005] [PMID: 24596668]

Kiuchi, F.; Itano, Y.; Uchiyama, N.; Honda, G.; Tsubouchi, A.; Nakajima-Shimada, J.; Aoki, T. Monoterpene hydroperoxides with trypanocidal activity from Chenopodium ambrosioides. J. Nat. Prod., 2002, 65(4), 509-512.
[http://dx.doi.org/10.1021/np010445g] [PMID: 11975490]

Monzote, L.; Montalvo, A.M.; Almanonni, S.; Scull, R.; Miranda, M.; Abreu, J. Activity of the essential oil from Chenopodium ambrosioides grown in Cuba against Leishmania amazonensis. Chemotherapy, 2006, 52(3), 130-136.
[http://dx.doi.org/10.1159/000092858] [PMID: 16636536]

Gildmeister, E.; Hoffmann, Fr. Die Atherishen Ole. Vol. IV; Beschreibung der einzelnen ätherischen Öle. (Spezieller Teil B; Vol. IV).. Academic-Verlag: Berlin,, 1956.

Wallach, O. Zur Kenntnis der terpene und der ätherischen öle. Justus Liebigs Ann. Chem., 1912, 392(1), 49-75.
[http://dx.doi.org/10.1002/jlac.19123920104]

Nelson, E.K. The composition of oil of Chenopodium from various sources. J. Am. Chem. Soc., 1920, 42(6), 1204-1208.
[http://dx.doi.org/10.1021/ja01451a016]

Smillie, W.G.; Pessôa, S.B. A study of the anthelmintic properties of the constituents of the oil of Chenopodium. J. Pharmacol. Exp. Ther., 1924, 24(5), 359-370.

Bodendorf, K. Über ungesättigte peroxyde. Zugleich ein beitrag zur kenntnis der autoxydationsvorgänge. Arch. Pharm. (Weinheim), 1933, 271(1), 1-35.
[http://dx.doi.org/10.1002/ardp.19332710102]

Beckett, A.H.; Donbrow, M.; Jolliffe, G.O. Ascaridole studies. III. The purification and characterisation of ascaridole. J. Pharm. Pharmacol., 1955, 7(1), 55-65.
[http://dx.doi.org/10.1111/j.2042-7158.1955.tb12006.x] [PMID: 13222253]

Beckett, A.H.; Jolliffe, G.O. A note on the determination of ascaridole in oil of chenopodium. J. Pharm. Pharmacol., 1955, 7(9), 606-607.
[http://dx.doi.org/10.1111/j.2042-7158.1955.tb12074.x] [PMID: 13264074]

Schenck, G.O.; Ziegler, K. Die synthese des ascaridols.. Naturwissenschaften, 1944, 32(14), 157-157.m.
[http://dx.doi.org/10.1007/BF01467891]

Pape, M. Industrial applications of photochemistry. Pure Appl. Chem., 1975, 41(4), 535-558.
[http://dx.doi.org/10.1351/pac197541040535]

Aubry, J-M.; Bouttemy, S. Preparative oxidation of organic compounds in microemulsions with singlet oxygen generated chemically by the sodium molybdate/hydrogen peroxide system. J. Am. Chem. Soc., 1997, 119(23), 5286-5294.
[http://dx.doi.org/10.1021/ja9644079]

MacDonald, D.; VanCrey, K.; Harrison, P.; Rangachari, P.K.; Rosenfeld, J.; Warren, C.; Sorger, G. Ascaridole-less infusions of Chenopodium ambrosioides contain a nematocide(s) that is(are) not toxic to mammalian smooth muscle. J. Ethnopharmacol., 2004, 92(2-3), 215-221.
[http://dx.doi.org/10.1016/j.jep.2004.02.018] [PMID: 15138003]

Yao, G.; Steliou, K. Synthetic studies toward bioactive cyclic peroxides from the marine sponge Plakortis angulospiculatus. Org. Lett., 2002, 4(4), 485-488.
[http://dx.doi.org/10.1021/ol016943y] [PMID: 11843572]

Xiao, S.; Tanner, M.; N’Goran, E.K.; Utzinger, J.; Chollet, J.; Bergquist, R.; Chen, M.; Zheng, J. Recent investigations of artemether, a novel agent for the prevention of schistosomiasis japonica, mansoni and haematobia. Acta Trop., 2002, 82(2), 175-181.
[http://dx.doi.org/10.1016/S0001-706X(02)00009-8] [PMID: 12020890]

Adekunle, A.S.; Falade, C.O.; Agbedana, E.O.; Egbe, A. Assessment of side-effects of administration of artemether in humans. Biol. Med. (Aligarh), 2009, 1(3), 15-19.
[http://dx.doi.org/10.4172/0974-8369.1000028]

Adekunle, A.S.; Agbedana, E.O.; Oyewopo, O.; Adedeji, A.L.; Adebisi, J.A. Antispermatogenic effects of artemether: An animal model. Toxicol. Environ. Chem., 2009, 91(3), 511-519.
[http://dx.doi.org/10.1080/02772240802188072]

Li, Y-S.; Chen, H-G.; He, H-B.; Hou, X-Y.; Ellis, M.; McManus, D.P. A double-blind field trial on the effects of artemether on Schistosoma japonicum infection in a highly endemic focus in southern China. Acta Trop., 2005, 96(2-3), 184-190.
[http://dx.doi.org/10.1016/j.actatropica.2005.07.013] [PMID: 16112071]

O’Neill, J.F.; Johnston, R.C.; Halferty, L.; Hanna, R.E.B.; Brennan, G.P.; Fairweather, I. A comparative study on the impact of two artemisinin derivatives, artemether and artesunate, on the female reproductive system of Fasciola hepatica. Vet. Parasitol., 2015, 211(3-4), 182-194.
[http://dx.doi.org/10.1016/j.vetpar.2015.05.027] [PMID: 26093822]

O’Neill, J.F.; Johnston, R.C.; Halferty, L.; Hanna, R.E.B.; Brennan, G.P.; Fairweather, I. Disruption of spermatogenesis in the liver fluke, Fasciola hepatica by two artemisinin derivatives, artemether and artesunate. J. Helminthol., 2017, 91(1), 55-71.
[http://dx.doi.org/10.1017/S0022149X16000079] [PMID: 26979164]

Keiser, J.; Sayed, H.; el-Ghanam, M.; Sabry, H.; Anani, S.; el-Wakeel, A.; Hatz, C.; Utzinger, J.; el-Din, S.S.; el-Maadawy, W.; Botros, S. Efficacy and safety of artemether in the treatment of chronic fascioliasis in Egypt: exploratory phase-2 trials. PLoS Negl. Trop. Dis., 2011, 5(9)e1285
[http://dx.doi.org/10.1371/journal.pntd.0001285] [PMID: 21909440]

Haynes, R.K.; Vonwiller, S.C. Extraction of artemisinin and artemisinic acid: Preparation of artemether and new analogues. Trans. R. Soc. Trop. Med. Hyg., 1994, 88(Suppl. 1), S23-S26.
[http://dx.doi.org/10.1016/0035-9203(94)90466-9] [PMID: 8053018]

Stringham, R.W.; Teager, D.S. Streamlined process for the conversion of artemisinin to artemether. Org. Process Res. Dev., 2012, 16(5), 764-768.
[http://dx.doi.org/10.1021/op300037e]

Gilmore, K.; Kopetzki, D.; Lee, J.W.; Horváth, Z.; McQuade, D.T.; Seidel-Morgenstern, A.; Seeberger, P.H. Continuous synthesis of artemisinin-derived medicines. Chem. Commun. (Camb.), 2014, 50(84), 12652-12655.
[http://dx.doi.org/10.1039/C4CC05098C] [PMID: 25204815]

Yaseneva, P.; Plaza, D.; Fan, X.; Loponov, K.; Lapkin, A. Synthesis of the antimalarial API artemether in a flow reactor. Catal. Today, 2015, 239, 90-96.
[http://dx.doi.org/10.1016/j.cattod.2014.04.014]

Li, S.; Wu, L.; Liu, Z.; Hu, L.; Xu, P.; Xuan, Y.; Liu, Y.; Liu, X.; Fan, J. Studies on prophylactic effect of artesunate on schistosomiasis japonica. Chin. Med. J. (Engl.), 1996, 109(11), 848-853.
[PMID: 9275368]

Liu, R.; Dong, H-F.; Guo, Y.; Zhao, Q-P.; Jiang, M-S. Efficacy of praziquantel and artemisinin derivatives for the treatment and prevention of human schistosomiasis: a systematic review and meta-analysis. Parasit. Vectors, 2011, 4, 201-201.
[http://dx.doi.org/10.1186/1756-3305-4-201] [PMID: 22004571]

Hien, T.T.; Truong, N.T.; Minh, N.H.; Dat, H.D.; Dung, N.T.; Hue, N.T.; Dung, T.K.; Tuan, P.Q.; Campbell, J.I.; Farrar, J.J.; Day, J.N. A randomized controlled pilot study of artesunate versus triclabendazole for human fascioliasis in central Vietnam. Am. J. Trop. Med. Hyg., 2008, 78(3), 388-392.
[http://dx.doi.org/10.4269/ajtmh.2008.78.388] [PMID: 18337331]

Ingram, K.; Schiaffo, C.E.; Sittiwong, W.; Benner, E.; Dussault, P.H.; Keiser, J. In vitro and in vivo activity of 3-alkoxy-1,2-dioxolanes against Schistosoma mansoni. J. Antimicrob. Chemother., 2012, 67(8), 1979-1986.
[http://dx.doi.org/10.1093/jac/dks141] [PMID: 22553141]

Ingram, K.; Yaremenko, I.A.; Krylov, I.B.; Hofer, L.; Terent’ev, A.O.; Keiser, J. Identification of antischistosomal leads by evaluating bridged 1,2,4,5-tetraoxanes, alphaperoxides, and tricyclic monoperoxides. J. Med. Chem., 2012, 55(20), 8700-8711.
[http://dx.doi.org/10.1021/jm3009184] [PMID: 23013253]

Terent’ev, A.O.; Yaremenko, I.A.; Chernyshev, V.V.; Dembitsky, V.M.; Nikishin, G.I. Selective synthesis of cyclic peroxides from triketones and H2O2. J. Org. Chem., 2012, 77(4), 1833-1842.
[http://dx.doi.org/10.1021/jo202437r] [PMID: 22263693]

Terent’ev, A.O.; Yaremenko, I.A.; Vil’, V.A.; Dembitsky, V.M.; Nikishin, G.I. Boron trifluoride as an efficient catalyst for the selective synthesis of tricyclic monoperoxides from β,δ-triketones and H2O2. Synthesis, 2013, 45(02), 246-250.
[http://dx.doi.org/10.1055/s-0032-1317895]

Keiser, J.; Utzinger, J.; Tanner, M.; Dong, Y.; Vennerstrom, J.L. The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica. J. Antimicrob. Chemother., 2006, 58(6), 1193-1197.
[http://dx.doi.org/10.1093/jac/dkl408] [PMID: 17028093]

Keiser, J.; Utzinger, J.; Vennerstrom, J.L.; Dong, Y.; Brennan, G.; Fairweather, I. Activity of artemether and OZ78 against triclabendazole-resistant Fasciola hepatica. Trans. R. Soc. Trop. Med. Hyg., 2007, 101(12), 1219-1222.
[http://dx.doi.org/10.1016/j.trstmh.2007.07.012] [PMID: 17905370]

Keiser, J.; Kirchhofer, C.; Haschke, M.; Huwyler, J.; Dong, Y.; Vennerstrom, J.L.; Vanhoff, K.; Kaminsky, R.; Malikides, N. Efficacy, safety and pharmacokinetics of 1,2,4-trioxolane OZ78 against an experimental infection with Fasciola hepatica in sheep. Vet. Parasitol., 2010, 173(3-4), 228-235.
[http://dx.doi.org/10.1016/j.vetpar.2010.06.031] [PMID: 20674178]

Meister, I.; Duthaler, U.; Huwyler, J.; Rinaldi, L.; Bosco, A.; Cringoli, G.; Keiser, J. Efficacy and pharmacokinetics of OZ78 and MT04 against a natural infection with Fasciola hepatica in sheep. Vet. Parasitol., 2013, 198(1-2), 102-110.
[http://dx.doi.org/10.1016/j.vetpar.2013.08.007] [PMID: 24011678]

Zhao, Q.; Vargas, M.; Dong, Y.; Zhou, L.; Wang, X.; Sriraghavan, K.; Keiser, J.; Vennerstrom, J.L. Structure-activity relationship of an ozonide carboxylic acid (OZ78) against Fasciola hepatica. J. Med. Chem., 2010, 53(10), 4223-4233.
[http://dx.doi.org/10.1021/jm100226t] [PMID: 20423101]

Xiao, S-H.; Keiser, J.; Chollet, J.; Utzinger, J.; Dong, Y.; Endriss, Y.; Vennerstrom, J.L.; Tanner, M. In vitro and in vivo activities of synthetic trioxolanes against major human schistosome species. Antimicrob. Agents Chemother., 2007, 51(4), 1440-1445.
[http://dx.doi.org/10.1128/AAC.01537-06] [PMID: 17283188]

Xiao, S.H.; Mei, J.Y.; Jiao, P.Y. Schistosoma japonicum-infected hamsters (Mesocricetus auratus) used as a model in experimental chemotherapy with praziquantel, artemether, and OZ compounds. Parasitol. Res., 2011, 108(2), 431-437.
[http://dx.doi.org/10.1007/s00436-010-2084-7] [PMID: 20922422]

Xiao, S.H.; Xue, J.; Mei, J.Y.; Jiao, P.Y. Effectiveness of synthetic trioxolane OZ78 against Schistosoma japonicum in mice and rabbits. Parasitol. Res., 2012, 110(6), 2307-2314.
[http://dx.doi.org/10.1007/s00436-011-2765-x] [PMID: 22200956]

Keiser, J.; Ingram, K.; Vargas, M.; Chollet, J.; Wang, X.; Dong, Y.; Vennerstrom, J.L. In vivo activity of aryl ozonides against Schistosoma species. Antimicrob. Agents Chemother., 2012, 56(2), 1090-1092.
[http://dx.doi.org/10.1128/AAC.05371-11] [PMID: 22106214]

Xue, J.; Wang, X.; Dong, Y.; Vennerstrom, J.L.; Xiao, S.H. Effect of ozonide OZ418 against Schistosoma japonicum harbored in mice. Parasitol. Res., 2014, 113(9), 3259-3266.
[http://dx.doi.org/10.1007/s00436-014-3988-4] [PMID: 24948106]

Griesbaum, K.; Övez, B.; Huh, T.S.; Dong, Y. Ozonolyses of O-methyloximes in the presence of acid derivatives: A new access to substituted ozonides. Liebigs Ann., 1995, 1995(8), 1571-1574.
[http://dx.doi.org/10.1002/jlac.1995199508217]

Griesbaum, K.; Liu, X.; Kassiaris, A.; Scherer, M. Ozonolyses of O-alkylated ketoximes in the presence of carbonyl groups: a facile access to ozonides. Liebigs Ann., 1997, 1997(7), 1381-1390.
[http://dx.doi.org/10.1002/jlac.199719970715]

Tang, Y.; Dong, Y.; Karle, J.M.; DiTusa, C.A.; Vennerstrom, J.L. Synthesis of tetrasubstituted ozonides by the Griesbaum coozonolysis reaction: diastereoselectivity and functional group transformations by post-ozonolysis reactions. J. Org. Chem., 2004, 69(19), 6470-6473.
[http://dx.doi.org/10.1021/jo040171c] [PMID: 15357611]

Dong, Y.; Chollet, J.; Matile, H.; Charman, S.A.; Chiu, F.C.K.; Charman, W.N.; Scorneaux, B.; Urwyler, H.; Santo Tomas, J.; Scheurer, C.; Snyder, C.; Dorn, A.; Wang, X.; Karle, J.M.; Tang, Y.; Wittlin, S.; Brun, R.; Vennerstrom, J.L. Spiro and dispiro-1,2,4-trioxolanes as antimalarial peroxides: charting a workable structure-activity relationship using simple prototypes. J. Med. Chem., 2005, 48(15), 4953-4961.
[http://dx.doi.org/10.1021/jm049040u] [PMID: 16033274]

Wang, X.; Zhao, Q.; Vargas, M.; Dong, Y.; Sriraghavan, K.; Keiser, J.; Vennerstrom, J.L. The activity of dispiro peroxides against Fasciola hepatica. Bioorg. Med. Chem. Lett., 2011, 21(18), 5320-5323.
[http://dx.doi.org/10.1016/j.bmcl.2011.07.024] [PMID: 21802291]

Amewu, R.; Stachulski, A.V.; Ward, S.A.; Berry, N.G.; Bray, P.G.; Davies, J.; Labat, G.; Vivas, L.; O’Neill, P.M. Design and synthesis of orally active dispiro 1,2,4,5-tetraoxanes; synthetic antimalarials with superior activity to artemisinin. Org. Biomol. Chem., 2006, 4(24), 4431-4436.
[http://dx.doi.org/10.1039/b613565j] [PMID: 17268634]

Duan, W.W.; Qiu, S.J.; Zhao, Y.; Sun, H.; Qiao, C.; Xia, C.M. Praziquantel derivatives exhibit activity against both juvenile and adult Schistosoma japonicum. Bioorg. Med. Chem. Lett., 2012, 22(4), 1587-1590.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.133] [PMID: 22264473]

Yang, J.J.; Boissier, J.; Chen, J-L.; Yao, H.; Yang, S.; Rognon, A.; Qiao, C. Design, synthesis and biological evaluation of praziquantel and endoperoxide conjugates as antischistosomal agents. Future Med. Chem., 2015, 7(6), 713-725.
[http://dx.doi.org/10.4155/fmc.15.20] [PMID: 25996065]

Cowan, N.; Yaremenko, I.A.; Krylov, I.B.; Terent’ev, A.O.; Keiser, J. 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. Bioorg. Med. Chem., 2015, 23(16), 5175-5181.
[http://dx.doi.org/10.1016/j.bmc.2015.02.010] [PMID: 25744189]

Terent’ev, A.O.; Borisov, D.A.; Chernyshev, V.V.; Nikishin, G.I. Facile and selective procedure for the synthesis of bridged 1,2,4,5-tetraoxanes; strong acids as cosolvents and catalysts for addition of hydrogen peroxide to β-diketones. J. Org. Chem., 2009, 74(9), 3335-3340.
[http://dx.doi.org/10.1021/jo900226b] [PMID: 19298073]

Terent’ev, A.O.; Yaremenko, I.A.; Vil’, V.A.; Moiseev, I.K.; Kon’kov, S.A.; Dembitsky, V.M.; Levitsky, D.O.; Nikishin, G.I. Phosphomolybdic and phosphotungstic acids as efficient catalysts for the synthesis of bridged 1,2,4,5-tetraoxanes from β-diketones and hydrogen peroxide. Org. Biomol. Chem., 2013, 11(16), 2613-2623.
[http://dx.doi.org/10.1039/c3ob27239g] [PMID: 23446630]

Murray, H.W.; Berman, J.D.; Davies, C.R.; Saravia, N.G. Advances in leishmaniasis. Lancet, 2005, 366(9496), 1561-1577.
[http://dx.doi.org/10.1016/S0140-6736(05)67629-5] [PMID: 16257344]

Croft, S.L.; Sundar, S.; Fairlamb, A.H. Drug resistance in leishmaniasis. Clin. Microbiol. Rev., 2006, 19(1), 111-126.
[http://dx.doi.org/10.1128/CMR.19.1.111-126.2006] [PMID: 16418526]

Sundar, S.; Chatterjee, M. Visceral leishmaniasis - current therapeutic modalities. Indian J. Med. Res., 2006, 123(3), 345-352.
[PMID: 16778315]

Jones, J.L.; Kruszon-Moran, D.; Wilson, M.; McQuillan, G.; Navin, T.; McAuley, J.B. Toxoplasma gondii infection in the United States: seroprevalence and risk factors. Am. J. Epidemiol., 2001, 154(4), 357-365.
[http://dx.doi.org/10.1093/aje/154.4.357] [PMID: 11495859]

Coccaro, E.F.; Lee, R.; Groer, M.W.; Can, A.; Coussons-Read, M.; Postolache, T.T. Toxoplasma gondii infection: relationship with aggression in psychiatric subjects. J. Clin. Psychiatry, 2016, 77(3), 334-341.
[http://dx.doi.org/10.4088/JCP.14m09621] [PMID: 27046307]

Tenter, A.M.; Heckeroth, A.R.; Weiss, L.M. Toxoplasma gondii: From animals to humans. Int. J. Parasitol., 2000, 30(12-13), 1217-1258.
[http://dx.doi.org/10.1016/S0020-7519(00)00124-7] [PMID: 11113252]

Wei, H-X.; Wei, S-S.; Lindsay, D.S.; Peng, H-J. A Systematic review and meta-analysis of the efficacy of anti-Toxoplasma gondii medicines in humans. PLoS One, 2015, 10(9)e0138204
[http://dx.doi.org/10.1371/journal.pone.0138204] [PMID: 26394212]

Stich, A. Zoonoses - Infections Affecting Humans and Animals.In:Focus on Public Health Aspects; Sing, A., Ed.; Springer Netherlands: Dordrecht, 2015, pp. 785-799.

Kennedy, P.G.E. Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol., 2013, 12(2), 186-194.
[http://dx.doi.org/10.1016/S1474-4422(12)70296-X] [PMID: 23260189]

Nagle, A.S.; Khare, S.; Kumar, A.B.; Supek, F.; Buchynskyy, A.; Mathison, C.J.N.; Chennamaneni, N.K.; Pendem, N.; Buckner, F.S.; Gelb, M.H.; Molteni, V. Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis. Chem. Rev., 2014, 114(22), 11305-11347.
[http://dx.doi.org/10.1021/cr500365f] [PMID: 25365529]

Pastor, J.; García, M.; Steinbauer, S.; Setzer, W.N.; Scull, R.; Gille, L.; Monzote, L. Combinations of ascaridole, carvacrol, and caryophyllene oxide against Leishmania. Acta Trop., 2015, 145, 31-38.
[http://dx.doi.org/10.1016/j.actatropica.2015.02.002] [PMID: 25697866]

Geroldinger, G.; Tonner, M.; Hettegger, H.; Bacher, M.; Monzote, L.; Walter, M.; Staniek, K.; Rosenau, T.; Gille, L. Mechanism of ascaridole activation in Leishmania. Biochem. Pharmacol., 2017, 132, 48-62.
[http://dx.doi.org/10.1016/j.bcp.2017.02.023] [PMID: 28263719]

Vil’, V.A.; Yaremenko, I.A.; Ilovaisky, A.I.; Terent’ev, A.O. Synthetic strategies for peroxide ring construction in artemisinin. Molecules, 2017, 22(1), 117.
[http://dx.doi.org/10.3390/molecules22010117] [PMID: 28085073]

Kopetzki, D.; Lévesque, F.; Seeberger, P.H. A continuous-flow process for the synthesis of artemisinin. Chemistry, 2013, 19(17), 5450-5456.
[http://dx.doi.org/10.1002/chem.201204558] [PMID: 23520059]

Vonwiller, S.C.; Warner, J.A.; Mann, S.T.; Haynes, R.K. Copper(II) trifluoromethanesulfonate-induced cleavage oxygenation of allylic hydroperoxides derived from qinghao acid in the synthesis of qinghaosu derivatives: Evidence for the Intermediacy of Enols. J. Am. Chem. Soc., 1995, 117(45), 11098-11105.
[http://dx.doi.org/10.1021/ja00150a009]

Yang, D.M.; Liew, F.Y. Effects of qinghaosu (artemisinin) and its derivatives on experimental cutaneous leishmaniasis. Parasitology, 1993, 106(Pt 1), 7-11.
[http://dx.doi.org/10.1017/S0031182000074758] [PMID: 8479804]

Sen, R.; Bandyopadhyay, S.; Dutta, A.; Mandal, G.; Ganguly, S.; Saha, P.; Chatterjee, M. Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes. J. Med. Microbiol., 2007, 56(Pt 9), 1213-1218.
[http://dx.doi.org/10.1099/jmm.0.47364-0] [PMID: 17761485]

Mishina, Y.V.; Krishna, S.; Haynes, R.K.; Meade, J.C. Artemisinins inhibit Trypanosoma cruzi and Trypanosoma brucei rhodesiense in vitro growth. Antimicrob. Agents Chemother., 2007, 51(5), 1852-1854.
[http://dx.doi.org/10.1128/AAC.01544-06] [PMID: 17339374]

Ke, O.Y.; Krug, E.C.; Marr, J.J.; Berens, R.L. Inhibition of growth of Toxoplasma gondii by qinghaosu and derivatives. Antimicrob. Agents Chemother., 1990, 34(10), 1961-1965.
[http://dx.doi.org/10.1128/AAC.34.10.1961] [PMID: 2291661]

Jones-Brando, L.; D’Angelo, J.; Posner, G.H.; Yolken, R. In vitro inhibition of Toxoplasma gondii by four new derivatives of artemisinin. Antimicrob. Agents Chemother., 2006, 50(12), 4206-4208.
[http://dx.doi.org/10.1128/AAC.00793-06] [PMID: 17060514]

D’Angelo, J.G.; Bordón, C.; Posner, G.H.; Yolken, R.; Jones-Brando, L. Artemisinin derivatives inhibit Toxoplasma gondii in vitro at multiple steps in the lytic cycle. J. Antimicrob. Chemother., 2009, 63(1), 146-150.
[http://dx.doi.org/10.1093/jac/dkn451] [PMID: 18988681]

Menon, R.B.; Kannoth, M.M.; Tekwani, B.L.; Gut, J.; Rosenthal, P.J.; Avery, M.A. A new library of C-16 modified artemisinin analogs and evaluation of their anti-parasitic activities. Comb. Chem. High Throughput Screen., 2006, 9(10), 729-741.
[http://dx.doi.org/10.2174/138620706779026051] [PMID: 17168678]

Slade, D.; Galal, A.M.; Gul, W.; Radwan, M.M.; Ahmed, S.A.; Khan, S.I.; Tekwani, B.L.; Jacob, M.R.; Ross, S.A.; Elsohly, M.A. Antiprotozoal, anticancer and antimicrobial activities of dihydroartemisinin acetal dimers and monomers. Bioorg. Med. Chem., 2009, 17(23), 7949-7957.
[http://dx.doi.org/10.1016/j.bmc.2009.10.019] [PMID: 19879765]

Feng, Y.; Davis, R.A.; Sykes, M.; Avery, V.M.; Camp, D.; Quinn, R.J. Antitrypanosomal cyclic polyketide peroxides from the Australian marine sponge Plakortis sp. J. Nat. Prod., 2010, 73(4), 716-719.
[http://dx.doi.org/10.1021/np900535z] [PMID: 20235550]

Oli, S.; Abdelmohsen, U.R.; Hentschel, U.; Schirmeister, T. Identification of plakortide E from the Caribbean sponge Plakortis halichondroides as a trypanocidal protease inhibitor using bioactivity-guided fractionation. Mar. Drugs, 2014, 12(5), 2614-2622.
[http://dx.doi.org/10.3390/md12052614] [PMID: 24798927]

Rubio, B.K.; Tenney, K.; Ang, K-H.; Abdulla, M.; Arkin, M.; McKerrow, J.H.; Crews, P. The marine sponge Diacarnus bismarckensis as a source of peroxiterpene inhibitors of Trypanosoma brucei, the causative agent of sleeping sickness. J. Nat. Prod., 2009, 72(2), 218-222.
[http://dx.doi.org/10.1021/np800711a] [PMID: 19159277]

El Sayed, K.A.; Hamann, M.T.; Hashish, N.E.; Shier, W.T.; Kelly, M.; Khan, A.A. Antimalarial, antiviral, and antitoxoplasmosis norsesterterpene peroxide acids from the Red Sea sponge Diacarnus erythraeanus. J. Nat. Prod., 2001, 64(4), 522-524.
[http://dx.doi.org/10.1021/np000529+] [PMID: 11325240]

Otoguro, K.; Iwatsuki, M.; Ishiyama, A.; Namatame, M.; Nishihara-Tukashima, A.; Kiyohara, H.; Hashimoto, T.; Asakawa, Y.; Ōmura, S.; Yamada, H. In vitro antitrypanosomal activity of plant terpenes against Trypanosoma brucei. Phytochemistry, 2011, 72(16), 2024-2030.
[http://dx.doi.org/10.1016/j.phytochem.2011.07.015] [PMID: 21843897]

Bloodworth, A.J.; Bothwell, B.D.; Collins, A.N.; Maidwell, N.L. A short synthesis of naturally occurring and other analogues of plakinic acids that contain the 1, 2-dioxolane group. Tetrahedron Lett., 1996, 37(11), 1885-1888.
[http://dx.doi.org/10.1016/0040-4039(96)00143-8]

Dussault, P.H.; Liu, X. Lewis acid-mediated displacements of alkoxydioxolanes: synthesis of a 1,2-dioxolane natural product. Org. Lett., 1999, 1(9), 1391-1393.
[http://dx.doi.org/10.1021/ol990954y] [PMID: 10825987]

Dai, P.; Trullinger, T.K.; Liu, X.; Dussault, P.H. Asymmetric synthesis of 1,2-dioxolane-3-acetic acids: synthesis and configurational assignment of plakinic acid A. J. Org. Chem., 2006, 71(6), 2283-2292.
[http://dx.doi.org/10.1021/jo0522254] [PMID: 16526775]

Sun, X-Y.; Tian, X-Y.; Li, Z-W.; Peng, X-S.; Wong, H.N.C. Total synthesis of plakortide E and biomimetic synthesis of plakortone B. Chemistry, 2011, 17(21), 5874-5880.
[http://dx.doi.org/10.1002/chem.201003309] [PMID: 21491517]

Zhao, Q.; Wong, H.N.C. Synthetic studies toward plakortide E: application of the Feldman oxygenation to synthesis of highly substituted 1,2-dioxolanes. Tetrahedron, 2007, 63(27), 6296-6305.
[http://dx.doi.org/10.1016/j.tet.2007.02.121]

Jung, M.; Ham, J.; Song, J. First total synthesis of natural 6-epiplakortolide e. Org. Lett., 2002, 4(16), 2763-2765.
[http://dx.doi.org/10.1021/ol026285x] [PMID: 12153229]

Perry, T.L.; Dickerson, A.; Khan, A.A.; Kondru, R.K.; Beratan, D.N.; Wipf, P.; Kelly, M.; Hamann, M.T. New peroxylactones from the Jamaican sponge Plakinastrella onkodes, with inhibitory activity against the AIDS opportunistic parasitic infection Toxoplasma gondii. Tetrahedron, 2001, 57(8), 1483-1487.
[http://dx.doi.org/10.1016/S0040-4020(00)01134-0]

Xu, C.; Schwartz, C.; Raible, J.; Dussault, P.H. Asymmetric synthesis of 1,2-dioxanes: approaches to the peroxyplakoric acids. Tetrahedron, 2009, 65(47), 9680-9685.
[http://dx.doi.org/10.1016/j.tet.2009.09.068] [PMID: 20160918]

Gemma, S.; Gabellieri, E.; Sanna Coccone, S.; Martí, F.; Taglialatela-Scafati, O.; Novellino, E.; Campiani, G.; Butini, S. Synthesis of dihydroplakortin, 6-epi-dihydroplakortin, and their C10-desethyl analogues. J. Org. Chem., 2010, 75(7), 2333-2340.
[http://dx.doi.org/10.1021/jo1001559] [PMID: 20199093]

Barnych, B.; Vatèle, J-M. Total synthesis of seco-plakortolide E and (-)-ent-plakortolide I: absolute configurational revision of natural plakortolide I. Org. Lett., 2012, 14(2), 564-567.
[http://dx.doi.org/10.1021/ol203185f] [PMID: 22191515]

Holla, H.; Labaied, M.; Pham, N.; Jenkins, I.D.; Stuart, K.; Quinn, R.J. Synthesis of antitrypanosomal 1,2-dioxane derivatives based on a natural product scaffold. Bioorg. Med. Chem. Lett., 2011, 21(16), 4793-4797.
[http://dx.doi.org/10.1016/j.bmcl.2011.06.059] [PMID: 21757346]