Abstract
Parasitic diseases, caused by helminths (ascariasis, hookworm, trichinosis, and schistosomiasis) and protozoa (chagas, leishmaniasis, and amebiasis), are considered a serious public health problem in developing countries. Additionally, there is a limited arsenal of anti-parasitic drugs in the current pipeline and growing drug resistance. Therefore, there is a clear need for the discovery and development of new compounds that can compete and replace these drugs that have been controlling parasitic infections over the last decades. However, this approach is highly resource- intensive, expensive and time-consuming. Accordingly, a drug repositioning strategy of the existing drugs or drug-like molecules with known pharmacokinetics and safety profiles is alternatively being used as a fast approach towards the identification of new treatments. The artemisinins, mefloquine, tribendimidine, oxantel pamoate and doxycycline for the treatment of helminths, and posaconazole and hydroxymethylnitrofurazone for the treatment of protozoa are promising candidates. Therefore, traditional antiprotozoal drugs, which were developed in some cases decades ago, are a valid solution. Herein, we review the current status of traditional anti-helminthic and antiprotozoal drugs in terms of drug targets, mode of action, doses, adverse effects, and parasite resistance to define their suitability for repurposing strategies. Current antiparasitic drugs are not only still viable for the treatment of helminth and protozoan infections but are also important candidates for new pharmacological treatments.
Keywords: Parasitic diseases, helminths, protozoa, drugs, design, infections, treatments.
[http://dx.doi.org/10.1056/NEJM199605023341808] [PMID: 8602186]
[http://dx.doi.org/10.1056/NEJMoa066536] [PMID: 17582067]
[http://dx.doi.org/10.1016/j.ijpddr.2014.07.002] [PMID: 25516827]
[http://dx.doi.org/10.1016/j.ejmech.2018.06.040] [PMID: 30033393]
[http://dx.doi.org/10.1021/ja01468a052]
[http://dx.doi.org/10.5216/rpt.v46i2.47571]
[http://dx.doi.org/10.1016/0169-4758(90)90227-U]
[PMID: 1034351]
[http://dx.doi.org/10.1016/0020-7519(88)90175-0] [PMID: 3066771]
[http://dx.doi.org/10.14712/18059694.2017.44] [PMID: 28399389]
[http://dx.doi.org/10.1038/nrc1317] [PMID: 15057285]
[http://dx.doi.org/10.1158/1078-0432.CCR-05-1181] [PMID: 16551879]
[http://dx.doi.org/10.1016/0035-9203(82)90034-7] [PMID: 7080143]
[http://dx.doi.org/10.1517/14656566.5.12.2615] [PMID: 15571478]
[http://dx.doi.org/10.1016/j.bmc.2015.03.085] [PMID: 25936258]
[http://dx.doi.org/10.4269/ajtmh.1983.32.118] [PMID: 6824117]
[http://dx.doi.org/10.1017/S0022149X17000426] [PMID: 28716158]
[http://dx.doi.org/10.7326/0003-4819-91-4-582] [PMID: 484964]
[http://dx.doi.org/10.1128/CMR.13.2.207] [PMID: 10755998]
[http://dx.doi.org/10.3389/fmicb.2017.00535] [PMID: 28400768]
[http://dx.doi.org/10.2119/molmed.2017.00011] [PMID: 28386621]
[http://dx.doi.org/10.1016/j.tiv.2017.06.007] [PMID: 28606429]
[PMID: 12479701]
[http://dx.doi.org/10.1093/neuonc/nor077] [PMID: 21764822]
[http://dx.doi.org/10.1016/0035-9203(83)90199-2] [PMID: 6659046]
[http://dx.doi.org/10.1345/aph.1D325] [PMID: 14749518]
[http://dx.doi.org/10.1371/journal.pntd.0006436] [PMID: 30650160]
[http://dx.doi.org/10.1586/eri.11.30] [PMID: 21609260]
[http://dx.doi.org/10.1016/j.ijpddr.2015.09.001] [PMID: 27120064]
[http://dx.doi.org/10.1038/srep08202] [PMID: 25644037]
[http://dx.doi.org/10.18632/oncotarget.3436] [PMID: 25811972]
[http://dx.doi.org/10.1039/C5MB00466G] [PMID: 26299935]
[PMID: 3533299]
[http://dx.doi.org/10.1016/j.actatropica.2009.11.001] [PMID: 19931502]
[http://dx.doi.org/10.3346/jkms.2008.23.5.903] [PMID: 18955802]
[http://dx.doi.org/10.1016/0035-9203(90)90324-8] [PMID: 2136253]
[http://dx.doi.org/10.1016/j.actatropica.2015.09.023] [PMID: 26476393]
[PMID: 27858056]
[http://dx.doi.org/10.7326/0003-4819-145-1-200607040-00009] [PMID: 16818928]
[http://dx.doi.org/10.1016/S1473-3099(14)70779-0] [PMID: 24999157]
[http://dx.doi.org/10.1186/1748-717X-6-160] [PMID: 22094106]
[http://dx.doi.org/10.1016/S0304-3835(01)00382-2] [PMID: 11248417]
[http://dx.doi.org/10.1007/s00280-004-0927-6] [PMID: 15565325]
[http://dx.doi.org/10.3892/etm.2016.3992] [PMID: 28352336]
[http://dx.doi.org/10.18632/oncotarget.17292] [PMID: 29069723]
[http://dx.doi.org/10.1128/AAC.15.3.361] [PMID: 464561]
[http://dx.doi.org/10.1021/jm00184a014] [PMID: 6893469]
[http://dx.doi.org/10.1016/j.pt.2017.02.004] [PMID: 28285851]
[http://dx.doi.org/10.1002/14651858.CD007745.pub3] [PMID: 26778150]
[PMID: 12077614]
[http://dx.doi.org/10.1179/000349802125002374] [PMID: 12630391]
[http://dx.doi.org/10.1016/j.bmc.2008.12.003] [PMID: 19114308]
[http://dx.doi.org/10.1016/j.clindermatol.2005.11.008] [PMID: 16714198]
[http://dx.doi.org/10.1111/j.1365-4632.2004.02253.x] [PMID: 16409259]
[http://dx.doi.org/10.1016/0169-4758(85)90100-0]
[http://dx.doi.org/10.4269/ajtmh.17-0042] [PMID: 29210346]
[http://dx.doi.org/10.1186/s12936-017-1803-2] [PMID: 28434407]
[http://dx.doi.org/10.1093/infdis/jis184] [PMID: 22396598]
[http://dx.doi.org/10.1016/S0140-6736(94)91625-X] [PMID: 7907715]
[PMID: 29511601]
[http://dx.doi.org/10.1182/blood-2010-01-262675] [PMID: 20644115]
[http://dx.doi.org/10.1093/cid/civ882] [PMID: 26486704]
[http://dx.doi.org/10.1016/0166-6851(91)90125-P] [PMID: 1775151]
[http://dx.doi.org/10.1017/S0031182000075351] [PMID: 1308929]
[PMID: 13472422]
[http://dx.doi.org/10.1016/j.ejphar.2014.03.046] [PMID: 24726556]
[http://dx.doi.org/10.1016/j.idc.2012.03.004] [PMID: 22632645]
[http://dx.doi.org/10.1371/journal.pntd.0001917] [PMID: 23236526]
[http://dx.doi.org/10.1093/jac/dkt491] [PMID: 24390933]
[http://dx.doi.org/10.4155/fmc.15.11] [PMID: 25996063]
[http://dx.doi.org/10.4172/2157-7579.1000200]
[http://dx.doi.org/10.1007/s00436-012-3151-z] [PMID: 23052781]
[http://dx.doi.org/10.1371/journal.pone.0051721] [PMID: 23251610]
[PMID: 3542267]
[http://dx.doi.org/10.1016/0169-4758(90)90215-P]
[http://dx.doi.org/10.1017/S003118200004662X] [PMID: 1187180]
[http://dx.doi.org/10.1016/S0306-3623(96)00149-8] [PMID: 9013207]
[http://dx.doi.org/10.1016/0020-7519(90)90198-V] [PMID: 2210944]
[http://dx.doi.org/10.1016/j.molbiopara.2011.01.012] [PMID: 21295079]
[http://dx.doi.org/10.1016/j.virusres.2018.07.018] [PMID: 30055216]
[http://dx.doi.org/10.1186/1477-3163-2-9] [PMID: 14624698]
[http://dx.doi.org/10.1016/j.imlet.2013.07.004] [PMID: 23891850]
[http://dx.doi.org/10.1046/j.1365-3156.2001.00819.x] [PMID: 11703837]
[http://dx.doi.org/10.1128/aac.32.6.799] [PMID: 3046480]
b)Slater, A.F.G.; Cerami, A. Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature, 1992, 355(6356), 167-169.
[http://dx.doi.org/10.1038/355167a0] [PMID: 1729651]
[http://dx.doi.org/10.1016/j.ebiom.2017.09.034] [PMID: 29033372]
[http://dx.doi.org/10.1016/j.celrep.2016.12.051] [PMID: 28076793]
[http://dx.doi.org/apps.who.int/medicinedocs/documents/s21839en/s21839en.pdf (Accessed Date: 13th September, 2017)]
[http://dx.doi.org/10.2217/14622416.9.10.1385] [PMID: 18855526]
[http://dx.doi.org/10.1016/0035-9203(87)90311-7] [PMID: 3328330]
[http://dx.doi.org/10.1093/infdis/158.6.1368] [PMID: 3058821]
[http://dx.doi.org/10.1016/S0140-6736(05)66417-3] [PMID: 15850631]
[http://dx.doi.org/10.1038/s41598-017-11924-4] [PMID: 28900272]
[http://dx.doi.org/10.1371/journal.pone.0202436] [PMID: 30208056]
[http://dx.doi.org/10.1111/cns.12536] [PMID: 27012974]
[http://dx.doi.org/10.1073/pnas.1509742112] [PMID: 26124091]
[http://dx.doi.org/10.2307/3281795] [PMID: 3519918]
[http://dx.doi.org/10.1128/AAC.21.4.581] [PMID: 6979309]
[http://dx.doi.org/10.1016/0169-4758(95)80201-0]
[http://dx.doi.org/10.1016/0140-6736(93)92409-M] [PMID: 8096956]
[http://dx.doi.org/10.1016/S0140-6736(04)16767-6] [PMID: 15288742]
[http://dx.doi.org/10.1371/journal.pntd.0002975] [PMID: 25033291]
[http://dx.doi.org/10.1111/cas.13540] [PMID: 29453896]
[http://dx.doi.org/10.1016/j.bbamem.2010.08.009] [PMID: 20713019]
[http://dx.doi.org/10.4103/2224-3151.213793] [PMID: 28857064]
[http://dx.doi.org/10.1093/jac/dkv018] [PMID: 25693996]
[http://dx.doi.org/10.1186/1743-422X-10-177] [PMID: 23734580]
[PMID: 27069141]
[http://dx.doi.org/10.1017/S0031182000074746] [PMID: 8479795]
[http://dx.doi.org/10.1086/508667] [PMID: 17029130]
[http://dx.doi.org/10.1016/0006-2952(90)90256-K] [PMID: 2157443]
[http://dx.doi.org/10.1054/drup.2000.0157] [PMID: 11498396]
[http://dx.doi.org/10.1016/j.tmaid.2017.12.005] [PMID: 29242073]
[http://dx.doi.org/10.1093/clinids/24.3.422] [PMID: 9114194]
[http://dx.doi.org/10.18632/oncotarget.9122] [PMID: 27136895]
[http://dx.doi.org/10.3390/pharmaceutics10020060] [PMID: 29783757]
[http://dx.doi.org/10.1007/s10863-018-9755-y] [PMID: 29687367]
[http://dx.doi.org/10.1128/CMR.5.4.387] [PMID: 1423217]
[http://dx.doi.org/10.1016/0166-6851(88)90031-X] [PMID: 2830511]
[http://dx.doi.org/10.1186/s12936-015-0980-0] [PMID: 26555664]
[http://dx.doi.org/10.1186/s12936-017-1797-9] [PMID: 28407772]
[http://dx.doi.org/10.1016/j.jinf.2016.02.001] [PMID: 26880088]
[http://dx.doi.org/10.1177/0049475515624857] [PMID: 26748392]
[http://dx.doi.org/10.1080/00034983.1982.11687502] [PMID: 7082077]
[http://dx.doi.org/10.1038/srep41755] [PMID: 28155912]
[http://dx.doi.org/10.1080/15384101.2016.1241929] [PMID: 27753527]
[http://dx.doi.org/10.1016/j.actatropica.2014.02.012] [PMID: 24560964]
[http://dx.doi.org/10.1074/jbc.M309341200] [PMID: 14679210]
[http://dx.doi.org/10.1016/j.pt.2012.12.005] [PMID: 23375541]
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0750] [PMID: 24785412]
[PMID: 2675120]
[http://dx.doi.org/10.1016/bs.armc.2018.08.003]
[http://dx.doi.org/10.1016/j.antiviral.2017.04.016] [PMID: 28461070]
[http://dx.doi.org/10.1016/j.bbrc.2017.07.157] [PMID: 28760340]
[http://dx.doi.org/10.1016/j.pt.2003.09.008] [PMID: 14580961]
[http://dx.doi.org/10.1186/s13071-015-0896-0] [PMID: 26017164]
[http://dx.doi.org/10.1371/journal.pntd.0005910] [PMID: 28892476]
[http://dx.doi.org/10.2174/1568026616666160216152138] [PMID: 26881721]
[http://dx.doi.org/10.1086/511425]
[http://dx.doi.org/10.1016/0169-4758(93)90144-5]
[http://dx.doi.org/10.1021/ml200161t] [PMID: 24900434]
[http://dx.doi.org/10.1074/jbc.274.37.26051] [PMID: 10473552]
[PMID: 24714229]
[PMID: 4983545]
[http://dx.doi.org/10.1590/s0074-02762002000100001] [PMID: 11992141]
[http://dx.doi.org/10.1016/j.molbiopara.2005.12.001] [PMID: 16442642]
[http://dx.doi.org/10.1191/0960327106het653oa] [PMID: 16937919]
[http://dx.doi.org/10.1093/cid/ciw477] [PMID: 27432838]
[http://dx.doi.org/10.1128/AAC.01401-12] [PMID: 23114763]
[http://dx.doi.org/10.1073/pnas.0711014105] [PMID: 18367671]
[PMID: 28560059]