Employing “Red Flags” to Fight the Most Neglected Diseases: Nitroaromatic as Still Suitable Tools to Treat Human and Veterinary Parasitosis

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Abstract

Nitroaromatic compounds have been used for treating parasitic diseases since the 1960s. Pharmacological alternatives to treat them are under observation. However, for the most neglected diseases, such as those caused by worms and less known protozoans, nitro compounds are still among the drugs of choice, despite their well-known collateral effects. In this review, we describe the chemistry and the uses of the still most employed nitroaromatic compounds for treating parasitosis caused by worms or lesser-known protozoans. We also describe their application as veterinary drugs. The most accepted mechanism of action seems to be the same, leading to collateral effects. For this reason, a special session was dedicated to discussing toxicity, carcinogenicity, and mutagenesis, as well as the most acceptable aspects of the known structure-activity/toxicity relationships involving nitroaromatic compounds. It employed the SciFindern search tool from the American Chemical Society in the search for the most relevant bibliography within the field, exploring keyword expressions such as “NITRO COMPOUNDS” and “BIOLOGICAL ACTIVITY” (within Abstracts or Keywords) and concepts related to parasites, pharmacology and toxicology. The results were classified according to the chemical classes of nitro compounds, being the most relevant studies regarding journal impact and interest of the described results chosen to be discussed. From the found literature, it is easy to notice that nitro compounds, especially the nitroaromatic ones, are still widely used in antiparasitic therapy, despite their toxicity. They also are the best starting point in the search for new active compounds.

Graphical Abstract

[1]
Mahmud, R.; Lim, Y.A.L.; Amir, A. Medical Parasitology; Springer International Publishing: Cham, 2017, pp. 1-4.
[http://dx.doi.org/10.1007/978-3-319-68795-7]
[2]
Ballweber, L.R. Introduction.Veterinary Parasitology; Ballweber, L.R., Ed.; Butterworth–Heinemann: Woburn, 2001, pp. 1-3.
[3]
de Moraes, J.; Geary, T.G. FDA-approved antiparasitic drugs in the 21st century: a success for helminthiasis? Trends Parasitol., 2020, 36(7), 573-575.
[http://dx.doi.org/10.1016/j.pt.2020.04.005] [PMID: 32387059]
[4]
Centers for Disease Control and Prevention. Parasites - Ascariasis.. Available from: https://www.cdc.gov/parasites/ascariasis/index.html
[5]
Mowlavi, G.; Massoud, J.; Mobedi, I.; Rezaian, M.; Solaymani Mohammadi, S.; Mostoufi, N. Enterobius vermicularis: A controversial cause of appendicitis. Iran. J. Public Health, 2004, 3333(3), 27-31.
[6]
Centers for Disease Control and Prevention. Parasites - Soil-transmitted helminths. 2022. Available from: https://www.cdc.gov/parasites/sth/index.html
[7]
Buonfrate, D.; Bisanzio, D.; Giorli, G.; Odermatt, P.; Fürst, T.; Greenaway, C.; French, M.; Reithinger, R.; Gobbi, F.; Montresor, A.; Bisoffi, Z. The global prevalence of Strongyloides stercoralis infection. Pathogens, 2020, 9(6), 468.
[http://dx.doi.org/10.3390/pathogens9060468] [PMID: 32545787]
[8]
Centers for Disease Control and Prevention. Hookworm (Intestinal); , 2019. Available from: https://www.cdc.gov/dpdx/hookworm/index.html
[9]
Einarsson, E.; Ma’ayeh, S.; Svärd, S.G. An up-date on Giardia and giardiasis. Curr. Opin. Microbiol., 2016, 34, 47-52.
[http://dx.doi.org/10.1016/j.mib.2016.07.019] [PMID: 27501461]
[10]
Song, L.G.; Wu, X.Y.; Sacko, M.; Wu, Z.D. History of schistosomiasis epidemiology, current status, and challenges in China: On the road to schistosomiasis elimination. Parasitol. Res., 2016, 115(11), 4071-4081.
[http://dx.doi.org/10.1007/s00436-016-5253-5] [PMID: 27679451]
[11]
World Health Organization. Global technical strategy for malaria 2016-2030; , 2015. Available from: https://www.who.int/publications-detail-redirect/9789240031357#:~:text=The%20strategy%20sets%20the%20target,over%20the%20last%205%20years
[12]
Van Gerwen, O.T.; Muzny, C.A. Recent advances in the epidemiology, diagnosis, and management of Trichomonas vaginalis infection. F1000 Res., 2019, 8, 1666.
[http://dx.doi.org/10.12688/f1000research.19972.1] [PMID: 31583080]
[13]
Kantor, M.; Abrantes, A.; Estevez, A.; Schiller, A.; Torrent, J.; Gascon, J.; Hernandez, R.; Ochner, C. Entamoeba Histolytica: Updates in Clinical Manifestation, Pathogenesis, and Vaccine Development. Can. J. Gastroenterol. Hepatol., 2018, 2018, 1-6.
[http://dx.doi.org/10.1155/2018/4601420] [PMID: 30631758]
[15]
World Health Organization. Chagas disease (American trypanosomiasis). Available from: https://www.who.int/health-topics/chagas-disease#tab=tab_1
[16]
World Health Organization. Taeniasis/cysticercosis. Available from: https://www.who.int/news-room/fact-sheets/detail/taeniasis-cysticercosis
[17]
World Health Organization. Leishmaniasis Available from: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis
[19]
Ferreira, L.L.G.; de Moraes, J.; Andricopulo, A.D. Approaches to advance drug discovery for neglected tropical diseases. Drug Discov. Today, 2022, 27(8), 2278-2287.
[http://dx.doi.org/10.1016/j.drudis.2022.04.004] [PMID: 35398562]
[20]
Geary, T.G.; Conder, G.A.; Bishop, B. The changing landscape of antiparasitic drug discovery for veterinary medicine. Trends Parasitol., 2004, 20(10), 449-455.
[http://dx.doi.org/10.1016/j.pt.2004.08.003] [PMID: 15363437]
[21]
Wishart, D.S. Nitro Compounds. Drug Bank Online. Available from: https://go.drugbank.com/categories/DBCAT000765
[22]
Wishart, D.S.; Feunang, Y.D.; Guo, A.C.; Lo, E.J.; Marcu, A.; Grant, J.R.; Sajed, T.; Johnson, D.; Li, C.; Sayeeda, Z.; Assempour, N.; Iynkkaran, I.; Liu, Y.; Maciejewski, A.; Gale, N.; Wilson, A.; Chin, L.; Cummings, R.; Le, D.; Pon, A.; Knox, C.; Wilson, M. DrugBank 5.0: A major update to the Drug Bank database for 2018. Nucleic Acids Res., 2018, 46(D1), D1074-D1082.
[http://dx.doi.org/10.1093/nar/gkx1037] [PMID: 29126136]
[23]
Patterson, S.; Fairlamb, A.H. Current and future prospects of nitro-compounds as drugs for Trypanosomiasis and Leishmaniasis. Curr. Med. Chem., 2019, 26(23), 4454-4475.
[http://dx.doi.org/10.2174/0929867325666180426164352] [PMID: 29701144]
[24]
Marozienė, A.; Lesanavičius, M.; Davioud-Charvet, E.; Aliverti, A.; Grellier, P.; Šarlauskas, J.; Čėnas, N. Antiplasmodial activity of nitroaromatic compounds: correlation with their reduction potential and inhibitory action on Plasmodium falciparum glutathione reductase. Molecules, 2019, 24(24), 4509.
[http://dx.doi.org/10.3390/molecules24244509] [PMID: 31835450]
[25]
Chemical Abstracts Service. SciFinder; Chemical Abstracts Service: Columbus 2022. Available from: https://scifinder.cas.org (accessed October, 21st, 2022).
[26]
Exner, O.; Krygowski, T.M. The nitro group as substituent. Chem. Soc. Rev., 1996, 25(1), 71.
[http://dx.doi.org/10.1039/cs9962500071]
[27]
Jezuita, A.; Ejsmont, K.; Szatylowicz, H. Substituent effects of nitro group in cyclic compounds. Struct. Chem., 2021, 32(1), 179-203.
[http://dx.doi.org/10.1007/s11224-020-01612-x]
[28]
Sukhorukov, A.Y. Editorial: Nitro compounds as versatile building blocks for the synthesis of pharmaceutically relevant substances. Front Chem., 2020, 8, 595246.
[http://dx.doi.org/10.3389/fchem.2020.595246] [PMID: 33195101]
[29]
Parry, R.; Nishino, S.; Spain, J. Naturally-occurring nitro compounds. Nat. Prod. Rep., 2011, 28(1), 152-167.
[http://dx.doi.org/10.1039/C0NP00024H] [PMID: 21127810]
[30]
Patterson, S; Fairlamb, AH Current and future prospects of nitrocompounds as drugs for trypanosomiasis and leishmaniasis. Curr Med Chem., 2019, 10; 26(23), 445475.
[31]
Spain, J.C. Biodegradation of nitroaromatic compounds. Annu. Rev. Microbiol., 1995, 49(1), 523-555.
[http://dx.doi.org/10.1146/annurev.mi.49.100195.002515] [PMID: 8561470]
[32]
Čênas, N.; Nemeikaité-Čéniené, A.; Sergedienè, E.; Nivinskas, H.; Anusevičius, Z.; Šarlauskas, J. Quantitative structure-activity relationships in enzymatic single-electron reduction of nitroaromatic explosives: Implications for their cytotoxicity. Biochim. Biophys. Acta, 2001, 1528(1), 31-38.
[http://dx.doi.org/10.1016/S0304-4165(01)00169-6] [PMID: 11514095]
[33]
Valiauga, B. Misevičienė, L.; Rich, M.H.; Ackerley, D.F.; Šarlauskas, J.; Čėnas, N. Mechanism of two-/four-electron reduction of nitroaromatics by oxygen-insensitive nitroreductases: the role of a non-enzymatic reduction step. Molecules, 2018, 23(7), 1672.
[http://dx.doi.org/10.3390/molecules23071672] [PMID: 29987261]
[34]
Whitmore, G.F.; Varghese, A.J. The biological properties of reduced nitroheterocyclics and possible underlying biochemical mechanisms. Biochem. Pharmacol., 1986, 35(1), 97-103.
[http://dx.doi.org/10.1016/0006-2952(86)90565-4] [PMID: 3510061]
[35]
Rossignol, J; Cavier, R. New dervatives of 2-benzamdo-5-nitro thazoles. Patent US3950351A, 1976.
[36]
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]
[37]
Rossignol, J.F.; Maisonneuve, H. Nitazoxanide in the treatment of Taenia saginata and Hymenolepis nana infections. Am. J. Trop. Med. Hyg., 1984, 33(3), 511-512.
[http://dx.doi.org/10.4269/ajtmh.1984.33.511] [PMID: 6731683]
[38]
Doumbo, O.; Rossignol, J.F.; Pichard, E.; Dembele, M.; Traore, H.A.; Diakite, M.; Traore, F.; Diallo, D.A. Nitazoxanide in the treatment of cryptosporidial diarrhea and other intestinal parasitic infections associated with acquired immunodeficiency syndrome in tropical Africa. Am. J. Trop. Med. Hyg., 1997, 56(6), 637-639.
[http://dx.doi.org/10.4269/ajtmh.1997.56.637] [PMID: 9230795]
[39]
Abaza, H.; El-Zayadi, A.R.; Kabil, S.M.; Rizk, H. Nitazoxanide in the treatment of patients with intestinal protozoan and helminthic infections: A report on 546 patients in Egypt. Curr. Ther. Res. Clin. Exp., 1998, 59(2), 116-121.
[http://dx.doi.org/10.1016/S0011-393X(98)85006-6]
[40]
Ortiz, J.J.; Chegne, N.L.; Gargala, G.; Favennec, L. Comparative clinical studies of nitazoxanide, albendazole and praziquantel in the treatment of ascariasis, trichuriasis and hymenolepiasis in children from Peru. Trans. R. Soc. Trop. Med. Hyg., 2002, 96(2), 193-196.
[http://dx.doi.org/10.1016/S0035-9203(02)90301-9] [PMID: 12055813]
[41]
Rossignol, J.F.; Abaza, H.; Friedman, H. Successful treatment of human fascioliasis with nitazoxanide. Trans. R. Soc. Trop. Med. Hyg., 1998, 92(1), 103-104.
[http://dx.doi.org/10.1016/S0035-9203(98)90974-9] [PMID: 9692168]
[42]
Esposito, M.; Stettler, R.; Moores, S.L.; Pidathala, C.; Müller, N.; Stachulski, A.; Berry, N.G.; Rossignol, J.F.; Hemphill, A. In vitro efficacies of nitazoxanide and other thiazolides against Neospora caninum tachyzoites reveal antiparasitic activity independent of the nitro group. Antimicrob. Agents Chemother., 2005, 49(9), 3715-3723.
[http://dx.doi.org/10.1128/AAC.49.9.3715-3723.2005] [PMID: 16127045]
[43]
Müller, J.; Müller, N.; Hemphill, A. Drugs and drug targets in neospora caninum and related apicomplexans. Apicomplexan Parasites; Wiley, 2011, pp. 359-371.
[http://dx.doi.org/10.1002/9783527633883.ch19]
[44]
McClure, S.R.; Palma, K.G. Treatment of equine protozoal myeloencephalitis with nitazoxanide. J. Equine Vet. Sci., 1999, 19(10), 639-641.
[http://dx.doi.org/10.1016/S0737-0806(06)82197-0]
[45]
Gargala, G.; Le Goff, L.; Ballet, J.J.; Favennec, L.; Stachulski, A.V.; Rossignol, J.F. In vitro efficacy of nitro- and halogeno-thiazolide/thiadiazolide derivatives against Sarcocystis neurona. Vet. Parasitol., 2009, 162(3-4), 230-235.
[http://dx.doi.org/10.1016/j.vetpar.2009.03.022] [PMID: 19369006]
[46]
Galván-Ramírez, M.L.; Dueñas Jiménez, J.M.; Rocío Rodríguez Pérez, L.; Troyo-Sanroman, R.; Ramírez-Herrera, M.; García-Iglesias, T. Effect of nitaxozanide and pyrimethamine on astrocytes infected by Toxoplasma gondii in vitro. Arch. Med. Res., 2013, 44(6), 415-421.
[http://dx.doi.org/10.1016/j.arcmed.2013.07.002] [PMID: 23973195]
[47]
El-Kowrany, S.I.; El Ghaffar, A.E.S.A.; Shoheib, Z.S.; Mady, R.F.; Gamea, G.A.M. Evaluation of nitazoxanide as a novel drug for the treatment of acute and chronic toxoplasmosis. Acta Trop., 2019, 195, 145-154.
[http://dx.doi.org/10.1016/j.actatropica.2019.04.013] [PMID: 30986380]
[48]
Anderson, V.R.; Curran, M.P. Nitazoxanide. Drugs, 2007, 67(13), 1947-1967.
[http://dx.doi.org/10.2165/00003495-200767130-00015] [PMID: 17722965]
[49]
Sisson, G.; Goodwin, A.; Raudonikiene, A.; Hughes, N.J.; Mukhopadhyay, A.K.; Berg, D.E.; Hoffman, P.S. Enzymes associated with reductive activation and action of nitazoxanide, nitrofurans, and metronidazole in Helicobacter pylori. Antimicrob. Agents Chemother., 2002, 46(7), 2116-2123.
[http://dx.doi.org/10.1128/AAC.46.7.2116-2123.2002] [PMID: 12069963]
[50]
Somvanshi, V.S.; Ellis, B.L.; Hu, Y.; Aroian, R.V. Nitazoxanide: Nematicidal mode of action and drug combination studies. Mol. Biochem. Parasitol., 2014, 193(1), 1-8.
[http://dx.doi.org/10.1016/j.molbiopara.2013.12.002] [PMID: 24412397]
[51]
Isac, E.; Picanço, G.A.; Costa, T.L.; Lima, N.F.; Alves, D.S.M.M.; Fraga, C.M.; Lino Junior, R.S.; Vinaud, M.C. In vitro nitazoxanide exposure affects energetic metabolism of Taenia crassiceps. Exp. Parasitol., 2020, 208, 107792.
[http://dx.doi.org/10.1016/j.exppara.2019.107792] [PMID: 31707003]
[52]
Atherton, R.R.D. Mechanisms of action of nitazoxanide and related drugs against helminths. PhD thesis. London School of Hygiene & Tropical Medicine, 2004.
[53]
Hemphill, A.; Muller, N.; Muller, J. Structure-function relationship of thiazolides, a novel class of anti-parasitic drugs, investigated in intracellular and extracellular protozoan parasites and larval-stage cestodes. Antiinfect. Agents Med. Chem., 2007, 6(4), 273-282.
[http://dx.doi.org/10.2174/187152107782023105]
[54]
Abdallah, A.; Saif, M. Clinical evaluation of niridazole in schistosoma haematobium and mansoni infections. Ann. N. Y. Acad. Sci., 1969, 160, 686-695.
[55]
Salem, H.H.; Hayaty, Z.G.; Awaness, A.M.; al-Allaf, G. The treatment of urinary schistosomiasis with Ambilhar in Mosul. J. Trop. Med. Hyg., 1969, 72(6), 137-142.
[PMID: 4891185]
[56]
Niridazole. Meyler’s Side Effects of Drugs; Elsevier, 2016, pp. 188-189.
[57]
Bulay, O.; Urman, H.; Clayson, D.B.; Shubik, P. Carcinogenic effects of niridazole on rodents infected with Schistosoma mansoni. J. Natl. Cancer Inst., 1977, 59(6), 1625-1630.
[http://dx.doi.org/10.1093/jnci/59.6.1625] [PMID: 926185]
[58]
Maeda, K.; Osato, T.; Umezawa, H. A new antibiotic, azomycin. J. Antibiot., 1953, 6(4), 182.
[PMID: 13152032]
[59]
Gupta, R.; Sharma, S.; Singh, R.; Vishwakarma, R.A.; Mignani, S.; Singh, P.P. Functionalized nitroimidazole scaffold construction and their pharmaceutical applications: a 1950–2021 comprehensive overview. Pharmaceuticals, 2022, 15(5), 561.
[http://dx.doi.org/10.3390/ph15050561] [PMID: 35631389]
[60]
Crespillo-Andújar, C.; Comeche, B.; Hamer, D.H.; Arevalo-Rodriguez, I.; Alvarez-Díaz, N.; Zamora, J.; Pérez-Molina, J.A. Use of benznidazole to treat chronic Chagas disease: An updated systematic review with a meta-analysis. PLoS Negl. Trop. Dis., 2022, 16(5), e0010386.
[http://dx.doi.org/10.1371/journal.pntd.0010386] [PMID: 35576215]
[61]
Pinheiro, E.; Brum-Soares, L.; Reis, R.; Cubides, J.C. Chagas disease: Review of needs, neglect, and obstacles to treatment access in Latin America. Rev. Soc. Bras. Med. Trop., 2017, 50(3), 296-300.
[http://dx.doi.org/10.1590/0037-8682-0433-2016] [PMID: 28700045]
[62]
Losada Galván, I.; Alonso-Padilla, J.; Cortés-Serra, N.; Alonso-Vega, C.; Gascón, J.; Pinazo, M.J. Benznidazole for the treatment of Chagas disease. Expert Rev. Anti Infect. Ther., 2021, 19(5), 547-556.
[http://dx.doi.org/10.1080/14787210.2021.1834849] [PMID: 33043726]
[63]
Tharmalingham, H.; Hoskin, P. Clinical trials targeting hypoxia. Br. J. Radiol., 2019, 92(1093), 20170966.
[PMID: 29979089]
[64]
Wardman, P. Nitroimidazoles as hypoxic cell radiosensitizers and hypoxia probes: Misonidazole, myths and mistakes. Br. J. Radiol., 2019, 92(1093), 20170915.
[PMID: 29303355]
[65]
Gardner, T.B.; Hill, D.R. Treatment of giardiasis. Clin. Microbiol. Rev., 2001, 14(1), 114-128.
[http://dx.doi.org/10.1128/CMR.14.1.114-128.2001] [PMID: 11148005]
[66]
Kaya, F. İnkaya, A.Ç.; Maçin, S.; Akyön, Y.; Ergüven, S. Refractory giardiasis in an immunosuppressed patient in turkey. J. Infect. Dev. Ctries., 2018, 12(3), 204-207.
[http://dx.doi.org/10.3855/jidc.9669] [PMID: 31829997]
[67]
Zimre-Grabensteiner, E.; Arshad, N.; Amin, A.; Hess, M. Genetically different clonal isolates of Trichomonas gallinae, obtained from the same bird, can vary in their drug susceptibility, an in vitro evidence. Parasitol. Int., 2011, 60(2), 213-215.
[http://dx.doi.org/10.1016/j.parint.2011.02.003] [PMID: 21345378]
[68]
Moreno, S.N.J.; Docampo, R. Reduction of 5-Nitroimidazoles, Nitrofurazone, and 2,4-dinitrophenol to their free radical metabolites by Tritrichomonas Foetus Hydrogenosomes. Oxygen Radicals in Biology and Medicine; Springer US: Boston, MA, 1988, pp. 759-764.
[http://dx.doi.org/10.1007/978-1-4684-5568-7_120]
[69]
Munoz, E.; Castella, J.; Gutierrez, J.F. In vivo and in vitro sensitivity of Trichomonas gallinae to some nitroimidazole drugs. Vet. Parasitol., 1998, 78(4), 239-246.
[http://dx.doi.org/10.1016/S0304-4017(98)00164-2] [PMID: 9786623]
[70]
Mtshali, A.; Ngcapu, S.; Govender, K.; Sturm, A.W.; Moodley, P.; Joubert, B.C. In vitro effect of 5-nitroimidazole drugs against Trichomonas vaginalis clinical isolates. Microbiol. Spectr., 2022, 10(4), e00912-e00922.
[http://dx.doi.org/10.1128/spectrum.00912-22] [PMID: 35863010]
[71]
Dans, L.F.; Martínez, E.G. Amoebic dysentery. BMJ Clin Evid, 2007, 2007, 0918.
[72]
Mackey-Lawrence, N.M.; Petri, W.A. Amoebic dysentery. BMJ Clin Evid, 2011, 2011, 0918.
[73]
Nagata, N.; Marriott, D.; Harkness, J.; Ellis, J.T.; Stark, D. In vitro susceptibility testing of Dientamoeba fragilis. Antimicrob. Agents Chemother., 2012, 56(1), 487-494.
[http://dx.doi.org/10.1128/AAC.05125-11] [PMID: 22024820]
[74]
Mirza, H.; Teo, J.D.W.; Upcroft, J.; Tan, K.S.W. A rapid, high-throughput viability assay for Blastocystis spp. reveals metronidazole resistance and extensive subtype-dependent variations in drug susceptibilities. Antimicrob. Agents Chemother., 2011, 55(2), 637-648.
[http://dx.doi.org/10.1128/AAC.00900-10] [PMID: 21098237]
[75]
Xin, Q.; Yuan, M.; Li, H.; Song, X.; Lu, J.; Jing, T. In vitro and in vivo effects of 3-bromopyruvate against Echinococcus metacestodes. Vet. Res., 2019, 50(1), 96.
[http://dx.doi.org/10.1186/s13567-019-0710-7] [PMID: 31744550]
[76]
Garcia-Laverde, A.; De Bonilla, L. Clinical trials with metronidazole in human balantidiasis. Am. J. Trop. Med. Hyg., 1975, 24(5), 781-783.
[http://dx.doi.org/10.4269/ajtmh.1975.24.781] [PMID: 1190365]
[77]
Cruz, C.C.P.; Ferrari, L.; Sogayar, R. Therapeutic trial on Giardia muris infection in mice with metronidazole, tinidazole, secnidazole and furazolidone. Rev. Soc. Bras. Med. Trop., 1997, 30(3), 223-228.
[http://dx.doi.org/10.1590/S0037-86821997000300009] [PMID: 9273569]
[78]
Marie, C; Petri, WA Amoebic dysentery. BMJ Clin Evid, 2013, 2013, 0918.
[79]
Mtshali, A.; Ngcapu, S.; Govender, K.; Sturm, AW.; Moodley, P.; Joubert, BC. In vitro effect of 5-nitroimidazole drugs against Trichomonas vaginalis clinical isolates. Microbiol Spectr., 2022, 31; 10(4)
[80]
Lamp, K.C.; Freeman, C.D.; Klutman, N.E.; Lacy, M.K. Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials. Clin. Pharmacokinet., 1999, 36(5), 353-373.
[http://dx.doi.org/10.2165/00003088-199936050-00004] [PMID: 10384859]
[81]
Jennings, F.W.; Urquhart, G.M. The use of the 2 substituted 5-nitroimidazole, fexinidazole (Hoe 239) in the treatment of chronicT. brucei infections in mice. Zeitschrift fur Parasitenkunde. Parasitol. Res., 1983, 69(5), 577-581.
[PMID: 6636983]
[82]
Pollastri, M.P. Fexinidazole: A new drug for african sleeping sickness on the horizon. Trends Parasitol., 2018, 34(3), 178-179.
[http://dx.doi.org/10.1016/j.pt.2017.12.002] [PMID: 29275007]
[83]
Kande Betu Ku Mesu, V.; Mutombo Kalonji, W.; Bardonneau, C.; Valverde Mordt, O.; Ngolo Tete, D.; Blesson, S.; Simon, F.; Delhomme, S.; Bernhard, S.; Mahenzi Mbembo, H.; Mpia Moke, C.; Lumeya Vuvu, S.; Mudji E’kitiak, J.; Akwaso Masa, F.; Mukendi Ilunga, M.; Mpoyi Muamba Nzambi, D.; Mayala Malu, T.; Kapongo Tshilumbwa, S.; Botalema Bolengi, F.; Nkieri Matsho, M.; Lumbala, C.; Scherrer, B.; Strub-Wourgaft, N.; Tarral, A. Oral fexinidazole for stage 1 or early stage 2 African Trypanosoma brucei gambiense trypanosomiasis: A prospective, multicentre, open-label, cohort study. Lancet Glob. Health, 2021, 9(7), e999-e1008.
[http://dx.doi.org/10.1016/S2214-109X(21)00208-4] [PMID: 34143998]
[84]
Burki, T. Fexinidazole recommended for sleeping sickness. Lancet Infect. Dis., 2019, 19(1), 30-31.
[http://dx.doi.org/10.1016/S1473-3099(18)30747-3] [PMID: 27998573]
[85]
Torreele, E.; Bourdin Trunz, B.; Tweats, D.; Kaiser, M.; Brun, R.; Mazué, G.; Bray, M.A.; Pécoul, B. Fexinidazole-a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Negl. Trop. Dis., 2010, 4(12), e923.
[http://dx.doi.org/10.1371/journal.pntd.0000923] [PMID: 21200426]
[86]
Torrico, F.; Gascón, J.; Ortiz, L.; Pinto, J.; Rojas, G.; Palacios, A. A phase 2, randomized, multicenter, placebo-controlled, proof-of-concept trial of oral fexinidazole in adults with chronic indeterminate chagas disease. Clin. Infect. Dis., 2022, 76(3), e1186-e1194.
[87]
Loser, D.; Grillberger, K.; Hinojosa, M.G.; Blum, J.; Haufe, Y.; Danker, T.; Johansson, Y.; Möller, C.; Nicke, A.; Bennekou, S.H.; Gardner, I.; Bauch, C.; Walker, P.; Forsby, A.; Ecker, G.F.; Kraushaar, U.; Leist, M. Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling. Arch. Toxicol., 2021, 95(12), 3695-3716.
[http://dx.doi.org/10.1007/s00204-021-03168-z] [PMID: 34628512]
[88]
Mikolić, A.; Karačonji, I.B. Imidacloprid as reproductive toxicant and endocrine disruptor: Investigations in laboratory animals. Arh. Hig. Rada Toksikol., 2018, 69(2), 103-108.
[http://dx.doi.org/10.2478/aiht-2018-69-3144] [PMID: 29990292]
[90]
Plumlee, K.H. Pharmaceuticals. Clinical Veterinary Toxicology; Elsevier, 2004, pp. 282-336.
[http://dx.doi.org/10.1016/B0-32-301125-X/50027-3]
[91]
Arther, R.G.; Charles, S.; Ciszewski, D.K.; Davis, W.L.; Settje, T.S. Imidacloprid/moxidectin topical solution for the prevention of heartworm disease and the treatment and control of flea and intestinal nematodes of cats. Vet. Parasitol., 2005, 133(2-3), 219-225.
[http://dx.doi.org/10.1016/j.vetpar.2005.04.001] [PMID: 16198823]
[92]
Arther, R.G.; Atkins, C.; Ciszewski, D.K.; Davis, W.L.; Ensley, S.M.; Settje, T.L. Safety of imidacloprid plus moxidectin topical solution applied to cats heavily infected with adult heartworms (Dirofilaria immitis). Parasitol. Res., 2005, 97(S1), S70-S75.
[http://dx.doi.org/10.1007/s00436-005-1447-y] [PMID: 16228278]
[93]
Arther, R.G.; Bowman, D.D.; Slone, R.L.; Travis, L.E. lmidacloprid plus moxidectin topical solution for the prevention of heartworm disease (Dirofiloria immitis) in dogs. Parasitol. Res., 2005, 97(S1), S76-S80.
[http://dx.doi.org/10.1007/s00436-005-1448-x] [PMID: 16228279]
[94]
Carter, E.R.; Nabarro, L.E.; Hedley, L.; Chiodini, P.L. Nitroimidazole-refractory giardiasis: A growing problem requiring rational solutions. Clin. Microbiol. Infect., 2018, 24(1), 37-42.
[http://dx.doi.org/10.1016/j.cmi.2017.05.028] [PMID: 28624613]
[95]
Townson, S.M.; Boreham, P.F.L.; Upcroft, P.; Upcroft, J.A. Resistance to the nitroheterocyclic drugs. Acta Trop., 1994, 56(2-3), 173-194.
[http://dx.doi.org/10.1016/0001-706X(94)90062-0] [PMID: 8203303]
[96]
Gillet, J.; Bruaux, P. Laboratory trials of the new molluscicides Bayer 73 and ICI 24223. Bull. World Health Organ., 1961, 25, 509-517.
[97]
Bruaux, P.; Gillet, J. Comparison of the activity of vaious molluscicides in the laboratory. Bull. World Health Organ., 1961, 25(4-5), 519-523.
[PMID: 13873804]
[98]
Gemmell, M.A.; Johnstone, P.D.; Oudemans, G. The effect of niclosamide on Echinococcus granulosus, Taenia hydatigena and Taenia ovis infections in dogs. Res. Vet. Sci., 1977, 22(3), 389-391.
[http://dx.doi.org/10.1016/S0034-5288(18)33273-9] [PMID: 877439]
[99]
Allen, R.W. Trials with Yomesan and other selected chemicals against Thysanosoma actinoides, the fringed tapeworm of sheep. Proc. Helminthol. Soc. Wash., 1967, 34(2), 195-199.
[100]
Mattila, M.; Takki, S. Metabolic effects of anthelmintic drugs on the cat’s tapeworm in vitro. Ann. Med. Exp. Biol. Fenn., 1966, 44(3), 415-418.
[PMID: 6006215]
[101]
Brown, H.W. Anthelmintics, new and old. Clin. Pharmacol. Ther., 1969, 10(1), 5-21.
[http://dx.doi.org/10.1002/cpt19691015] [PMID: 4303825]
[102]
Roberson, E.L. Comparative effects of uredofos, niclosamide, and bunamidine hydrochloride against tapeworm infections in dogs. Am. J. Vet. Res., 1976, 37(12), 1483-1484.
[PMID: 1033722]
[103]
Turton, J.A.; Williamson, J.R.; Harris, W.G. Haematological and immunological responses to the tapeworm hymenolepis diminuta in man. Tropenmed. Parasitol., 1975, 26(2), 196-200.
[PMID: 1162734]
[104]
Hughes, H.C., Jr; Barthel, C.H.; Lang, C.M. Niclosamide as a treatment for Hymenolepis nana and Hymenolepis diminuta in rats. Lab. Anim. Sci., 1973, 23(1), 72-73.
[PMID: 4347763]
[105]
Fomovska, A.; Wood, R.D.; Mui, E.; Dubey, J.P.; Ferreira, L.R.; Hickman, M.R.; Lee, P.J.; Leed, S.E.; Auschwitz, J.M.; Welsh, W.J.; Sommerville, C.; Woods, S.; Roberts, C.; McLeod, R. Salicylanilide inhibitors of Toxoplasma gondii. J. Med. Chem., 2012, 55(19), 8375-8391.
[http://dx.doi.org/10.1021/jm3007596] [PMID: 22970937]
[106]
Zhang, J.L.; Si, H.F.; Shang, X.F.; Zhang, X.K.; Li, B.; Zhou, X.Z.; Zhang, J.Y. New life for an old drug: in vitro and in vivo effects of the anthelmintic drug niclosamide against Toxoplasma gondii RH strain. Int. J. Parasitol. Drugs Drug Resist., 2019, 9, 27-34.
[http://dx.doi.org/10.1016/j.ijpddr.2018.12.004] [PMID: 30599391]
[107]
Chen, W.; Mook, R.A., Jr; Premont, R.T.; Wang, J. Niclosamide: Beyond an antihelminthic drug. Cell. Signal., 2018, 41, 89-96.
[http://dx.doi.org/10.1016/j.cellsig.2017.04.001] [PMID: 28389414]
[108]
Györke, A. Kalmár, Z.; Pop, L.M.; Şuteu, O.L. The economic impact of infection with Eimeria spp. in broiler farms from Romania. Rev. Bras. Zootec., 2016, 45(5), 273-280.
[http://dx.doi.org/10.1590/S1806-92902016000500010]
[109]
Beers, K.W.; Raup, T.J.; Bottje, W.G.; Odom, T.W. Physiological responses of heat-stressed broilers fed nicarbazin. Poult. Sci., 1989, 68(3), 428-434.
[http://dx.doi.org/10.3382/ps.0680428] [PMID: 2704700]
[110]
Lima, A.L.; Barreto, F.; Rau, R.B.; Silva, G.R.; Lara, L.J.C.; Figueiredo, T.C.; Assis, D.C.S.; Cançado, S.V. Determination of the residue levels of nicarbazin and combination nicarbazin-narasin in broiler chickens after oral administration. PLoS One, 2017, 12(7), e0181755.
[http://dx.doi.org/10.1371/journal.pone.0181755] [PMID: 28750013]
[111]
Bafundo, K.W.; Jeffers, T.K. Selection for resistance to monensin, nicarbazin, and the monensin plus nicarbazin combination. Poult. Sci., 1990, 69(9), 1485-1490.
[http://dx.doi.org/10.3382/ps.0691485] [PMID: 2247409]
[112]
Vereecken, M.; Dehaeck, B.; Berge, A.C.; Marien, M.; Geerinckx, M.; De Gussem, K. Synergistic effect of a combination of nicarbazin and monensin against coccidiosis in the chicken caused by Eimeria spp. Avian Pathol., 2020, 49(4), 389-393.
[http://dx.doi.org/10.1080/03079457.2020.1756226] [PMID: 32310002]
[113]
Peek, H.W.; Landman, W.J.M. Coccidiosis in poultry: Anticoccidial products, vaccines and other prevention strategies. Vet. Q., 2011, 31(3), 143-161.
[http://dx.doi.org/10.1080/01652176.2011.605247] [PMID: 22029884]
[114]
da Silva, V.B.R.; Campos, B.R.K.L.; de Oliveira, J.F.; Decout, J.L.; do Carmo Alves de Lima, M. Medicinal chemistry of antischistosomal drugs: Praziquantel and oxamniquine. Bioorg. Med. Chem., 2017, 25(13), 3259-3277.
[http://dx.doi.org/10.1016/j.bmc.2017.04.031] [PMID: 28495384]
[115]
Chevalier, F.D.; Le Clec’h, W.; McDew-White, M.; Menon, V.; Guzman, M.A.; Holloway, S.P.; Cao, X.; Taylor, A.B.; Kinung’hi, S.; Gouvras, A.N.; Webster, B.L.; Webster, J.P.; Emery, A.M.; Rollinson, D.; Garba Djirmay, A.; Al Mashikhi, K.M.; Al Yafae, S.; Idris, M.A.; Moné, H.; Mouahid, G.; Hart, P.J.; LoVerde, P.T.; Anderson, T.J.C. Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment. PLoS Pathog., 2019, 15(10), e1007881.
[http://dx.doi.org/10.1371/journal.ppat.1007881] [PMID: 31652296]
[116]
LoVerde, P.T.; Alwan, S.N.; Taylor, A.B.; Rhodes, J.; Chevalier, F.D.; Anderson, T.J.C.; McHardy, S.F. Rational approach to drug discovery for human schistosomiasis. Int. J. Parasitol. Drugs Drug Resist., 2021, 16, 140-147.
[http://dx.doi.org/10.1016/j.ijpddr.2021.05.002] [PMID: 34111649]
[117]
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]
[118]
Lerman, S.J.; Walker, R.A. Treatment of Giardiasis. Clin. Pediatr., 1982, 21(7), 409-414.
[http://dx.doi.org/10.1177/000992288202100704] [PMID: 7044642]
[119]
Loderstädt, U.; Frickmann, H. Antimicrobial resistance of the enteric protozoon Giardia duodenalis – A narrative review. Eur. J. Microbiol. Immunol., 2021, 11(2), 29-43.
[http://dx.doi.org/10.1556/1886.2021.00009] [PMID: 34237023]
[120]
Krantz, J.C., Jr; Evans, W.E. Jr A contribution to the pharmacology of 5-nitro-2-furaldehyde semicarbazone. J. Pharmacol. Exp. Ther., 1945, 85, 324-331.
[PMID: 21010739]
[121]
Vass, M.; Hruska, K.; Franek, M. Nitrofuran antibiotics: A review on the application, prohibition and residual analysis. Vet. Med., 2008, 53(9), 469-500.
[http://dx.doi.org/10.17221/1979-VETMED]
[122]
Fernando da Silva Santos-Júnior, P.; Rocha Silva, L.; José Quintans-Júnior, L.; Ferreira da Silva-Júnior, E. Nitro compounds against trypanosomatidae parasites: Heroes or villains? Bioorg. Med. Chem. Lett., 2022, 75, 128930.
[http://dx.doi.org/10.1016/j.bmcl.2022.128930] [PMID: 36030001]
[123]
Urbina, J. Chemotherapy of Chagas disease. Curr. Pharm. Des., 2002, 8(4), 287-295.
[http://dx.doi.org/10.2174/1381612023396177] [PMID: 11860367]
[124]
Alanazi, M.Q. Drugs may be induced methemoglobinemia. J. Hematol. Thromboembol. Dis., 2017, 6(1), 1-5.
[http://dx.doi.org/10.4172/2329-8790.1000270]
[125]
Huang, T.; Sun, G.; Zhao, L.; Zhang, N.; Zhong, R.; Peng, Y. Quantitative structure-activity relationship (QSAR) studies on the toxic effects of nitroaromatic compounds (NACs): a systematic review. Int. J. Mol. Sci., 2021, 22(16), 8557.
[http://dx.doi.org/10.3390/ijms22168557] [PMID: 34445263]
[126]
Mondal, D.; Ghosh, K.; Baidya, A.T.K.; Gantait, A.M.; Gayen, S. Identification of structural fingerprints for in vivo toxicity by using Monte Carlo based QSTR modeling of nitroaromatics. Toxicol. Mech. Methods, 2020, 30(4), 257-265.
[http://dx.doi.org/10.1080/15376516.2019.1709238] [PMID: 31876230]
[127]
Knox, R.J.; Knight, R.C.; Edwards, D.I. Interaction of nitroimidazole drugs with DNA in vitro: Structure-activity relationships. Br. J. Cancer, 1981, 44(5), 741-745.
[http://dx.doi.org/10.1038/bjc.1981.261] [PMID: 7032569]
[128]
Tocher, J.H. Reductive activation of nitroheterocyclic compounds. Gen. Pharmacol., 1997, 28(4), 485-487.
[http://dx.doi.org/10.1016/S0306-3623(96)00283-2] [PMID: 9147012]
[129]
Edwards, D.I.; Knox, R.J.; Knight, R.C. Structure-cytotoxicity relationships of nitroimidazoles in an in vitro system. Int. J. Radiat. Oncol. Biol. Phys., 1982, 8(3-4), 791-793.
[http://dx.doi.org/10.1016/0360-3016(82)90736-2]
[130]
Paulai, F.R.; Serrano, S.H.P.; Tavares, L.C. Mechanistic aspects of bioactivity and toxicity of nitrocompounds. Quim. Nova, 2009, 32(4), 1013-1020.
[http://dx.doi.org/10.1590/S0100-40422009000400032]
[131]
Hornberg, J.J.; Laursen, M.; Brenden, N.; Persson, M.; Thougaard, A.V.; Toft, D.B.; Mow, T. Exploratory toxicology as an integrated part of drug discovery. Part II: Screening strategies. Drug Discov. Today, 2014, 19(8), 1137-1144.
[http://dx.doi.org/10.1016/j.drudis.2013.12.009] [PMID: 24374152]
[132]
Huang, T; Sun, G; Zhao, L; Zhang, N; Zhong, R; Peng, Y. Quantitative structure-activity relationship (QSAR) studies on the toxic effects of nitroaromatic compounds (NACs): a systematic review. Int J Mol Sci., 2021, 9; 22(16), 8557.