Abstract
The use of nerve agents as warfare and in terrorist acts has drawn much attention from the governments and societies. Such toxic organophosphorus compounds are listed in Chemical Weapons Convention as Schedule 1 chemicals. The discussion about the chemical identity of the elusive Novichok agents, more potent compounds than best known G- and V-Agents, which have been implicated in recent rumorous assassination plots, clearly demonstrating the importance of the matter. Furthermore, accidents with pesticides or misuse thereof have been a pressing issue in many countries. In this context, the continued development of novel cholinesterase reactivators, antidotes for organophosphorus poisoning, a rather restricted class of pharmaceutical substances, is warranted. Testing of novel candidates may require use of actual nerve agents. Nonetheless, only a few laboratories comply with the requirements for storing, possession and manipulation of such toxic chemicals. To overcome such limitations, nerve agents’ surrogates may be a useful alternative, as they undergo the same reaction with cholinesterases, yielding similar adducts, allowing assays with novel antidote candidates, among other applications.
Keywords: Nerve Agents' surrogates, Cholinesterases, Drug development, Drug screening, Chemical Weapons Convention, Antidotes.
Graphical Abstract
[http://dx.doi.org/10.1016/B978-0-323-28665-7.00080-7]
[PMID: 30132046]
[http://dx.doi.org/10.1016/j.mpmed.2015.11.004]
[http://dx.doi.org/10.1590/S0103-50532009000300003]
[http://dx.doi.org/10.1097/00000441-200206000-00005] [PMID: 12074487]
[http://dx.doi.org/10.1016/j.toxlet.2017.11.040] [PMID: 29197625]
[http://dx.doi.org/10.1016/B978-0-12-386454-3.00635-7]
[http://dx.doi.org/10.1177/0960327117734620] [PMID: 29069930]
[http://dx.doi.org/10.1007/s00204-016-1772-1] [PMID: 27349770]
[http://dx.doi.org/10.1016/j.cca.2014.01.024] [PMID: 24508992]
[http://dx.doi.org/10.1038/363003b0] [PMID: 8479533]
[http://dx.doi.org/10.1503/cmaj.131359] [PMID: 24013089]
[http://dx.doi.org/10.1126/science.341.6150.1050] [PMID: 24009365]
[http://dx.doi.org/10.1503/cmaj.109-4592] [PMID: 24003104]
[http://dx.doi.org/10.1136/bmj.f5413] [PMID: 24002814]
[http://dx.doi.org/10.1017/S1049023X00000844] [PMID: 15074491]
[http://dx.doi.org/10.1016/j.jns.2006.06.007] [PMID: 16962140]
[http://dx.doi.org/10.1006/taap.1997.8110] [PMID: 9169085]
[http://dx.doi.org/10.2165/00139709-200524040-00006] [PMID: 16499408]
[http://dx.doi.org/10.3891/acta.chem.scand.11-1340]
[http://dx.doi.org/10.3891/acta.chem.scand.11-0859]
[http://dx.doi.org/10.1021/acschemneuro.8b00148] [PMID: 29664277]
[http://dx.doi.org/10.1016/S0140-6736(95)92306-3] [PMID: 7658832]
[http://dx.doi.org/10.1146/annurev.pa.34.040194.001433] [PMID: 8042853]
[http://dx.doi.org/10.1038/35067589] [PMID: 11283752]
[http://dx.doi.org/10.1016/j.coph.2005.01.014] [PMID: 15907917]
[http://dx.doi.org/10.1021/cr00081a005]
[http://dx.doi.org/10.1042/bj2600625] [PMID: 2669736]
[http://dx.doi.org/10.1016/0959-440X(92)90207-N]
[http://dx.doi.org/10.1016/j.cbi.2010.01.042] [PMID: 20138030]
[http://dx.doi.org/10.1016/S0009-2797(99)00014-9] [PMID: 10421439]
[http://dx.doi.org/10.1016/j.pharmthera.2014.11.011] [PMID: 25448037]
[http://dx.doi.org/10.1016/j.jconrel.2016.04.008] [PMID: 27063423]
[http://dx.doi.org/10.1021/bi0621361] [PMID: 17402711]
[http://dx.doi.org/10.1016/j.tox.2006.07.003] [PMID: 16904809]
[http://dx.doi.org/10.1016/j.cortex.2015.08.022] [PMID: 26493934]
[http://dx.doi.org/10.1016/j.toxlet.2015.11.023] [PMID: 26621540]
[PMID: 24807372]
[http://dx.doi.org/10.1016/j.fct.2018.09.015] [PMID: 30213549]
[http://dx.doi.org/10.3390/ijms20051222] [PMID: 30862059]
[http://dx.doi.org/10.1016/j.neuro.2006.04.006] [PMID: 16730798]
[http://dx.doi.org/10.1016/j.jns.2006.06.008] [PMID: 16945386]
[http://dx.doi.org/10.1016/B978-012374484-5.00065-1]
[http://dx.doi.org/10.1016/B978-012374484-5.00066-3]
[http://dx.doi.org/10.1016/j.cbi.2012.07.003] [PMID: 22827894]
[http://dx.doi.org/10.2174/138955706776073510] [PMID: 16515465]
[http://dx.doi.org/10.1080/13543776.2017.1338275] [PMID: 28569609]
[http://dx.doi.org/10.1007/s00204-016-1827-3] [PMID: 27582056]
[http://dx.doi.org/10.1016/0006-2952(89)90209-8] [PMID: 2917018]
[PMID: 6724203]
[http://dx.doi.org/10.1007/BF01981499] [PMID: 1482283]
[http://dx.doi.org/10.1111/j.1742-7843.2004.950207.x] [PMID: 15379785]
[http://dx.doi.org/10.1515/aiht-2015-66-2623] [PMID: 26110474]
[http://dx.doi.org/10.2174/1568026611209061775] [PMID: 23030612]
[http://dx.doi.org/10.1039/C5RA25477A]
[http://dx.doi.org/10.1073/pnas.97.13.7058] [PMID: 10860971]
[http://dx.doi.org/10.1002/chem.200902986] [PMID: 20143367]
[http://dx.doi.org/10.1016/j.jfluchem.2011.05.028]
[http://dx.doi.org/10.1016/j.bmcl.2008.12.070] [PMID: 19124241]
[http://dx.doi.org/10.1016/j.bmc.2009.07.043] [PMID: 19665386]
[http://dx.doi.org/10.1074/jbc.M111.230656] [PMID: 21464125]
[http://dx.doi.org/10.1021/jm401650z] [PMID: 24571195]
[http://dx.doi.org/10.1074/jbc.M111.333732] [PMID: 22343626]
[http://dx.doi.org/10.1042/BJ20121612] [PMID: 23216060]
[http://dx.doi.org/10.1016/j.cbi.2010.02.023] [PMID: 20206154]
[http://dx.doi.org/10.1016/j.cbi.2012.08.019] [PMID: 22960624]
[http://dx.doi.org/10.1007/s12630-017-0920-2] [PMID: 28766156]
[http://dx.doi.org/10.1111/epi.12989] [PMID: 26032507]
[http://dx.doi.org/10.1007/s40268-017-0219-3] [PMID: 29177587]
[http://dx.doi.org/10.1177/0885066603258659] [PMID: 15035752]
[http://dx.doi.org/10.1016/j.jconrel.2016.07.001] [PMID: 27397490]
[http://dx.doi.org/10.1111/j.1742-7843.2008.00326.x] [PMID: 19053994]
[http://dx.doi.org/10.3121/cmr.2007.701] [PMID: 17456837]
[http://dx.doi.org/10.1111/nyas.13028] [PMID: 27002925]
[http://dx.doi.org/10.1016/j.neuro.2009.06.011] [PMID: 19591865]
[http://dx.doi.org/10.1186/2008-2231-20-81] [PMID: 23351280]
[http://dx.doi.org/10.2174/1570159X11311030006] [PMID: 24179466]
[http://dx.doi.org/10.1042/bj3180833] [PMID: 8836126]
[http://dx.doi.org/10.1016/j.cbi.2010.03.027] [PMID: 20338153]
[http://dx.doi.org/10.1042/BJ20090091] [PMID: 19368529]
[http://dx.doi.org/10.1021/bi982678l] [PMID: 10353814]
[http://dx.doi.org/10.1016/j.cbi.2010.04.014] [PMID: 20412789]
[http://dx.doi.org/10.1021/jm900433t] [PMID: 19642642]
[http://dx.doi.org/10.1021/ja408585j] [PMID: 24063351]
[http://dx.doi.org/10.1039/c3cc44841j] [PMID: 23994877]
[http://dx.doi.org/10.1021/jacs.5b06041] [PMID: 26348904]
[http://dx.doi.org/10.1021/ja510477q] [PMID: 25402739]
[http://dx.doi.org/10.1021/jacs.5b06207] [PMID: 26356087]
[http://dx.doi.org/10.1002/chem.201602292] [PMID: 27859726]
[http://dx.doi.org/10.1039/C8CC06425C] [PMID: 30226513]
[http://dx.doi.org/10.1021/acsomega.9b00502]
[http://dx.doi.org/10.1093/toxsci/kfs013] [PMID: 22247004]
[http://dx.doi.org/10.1016/j.cbi.2016.07.004] [PMID: 27387540]
[http://dx.doi.org/10.1088/1742-6596/975/1/012020]
[http://dx.doi.org/10.1016/j.toxlet.2016.03.002] [PMID: 26965078]
[http://dx.doi.org/10.21577/0103-5053.20180246]
[http://dx.doi.org/10.1002/rcm.6596] [PMID: 23722680]
[http://dx.doi.org/10.1016/j.ijms.2015.12.004]
[http://dx.doi.org/10.1016/j.tetlet.2014.07.057]
[http://dx.doi.org/10.1002/cmdc.201800693]
[http://dx.doi.org/10.1080/10426500701792974]
[http://dx.doi.org/10.1021/ja01026a045]
[http://dx.doi.org/10.1055/s-1977-24435]
[http://dx.doi.org/10.1039/b006883g]
[http://dx.doi.org/10.1002/ange.19921041011]
[http://dx.doi.org/10.1016/0021-9673(94)80518-0] [PMID: 8143028]
[http://dx.doi.org/10.1016/j.jchromb.2017.05.005] [PMID: 28531843]
[http://dx.doi.org/10.1007/s00216-014-7695-x] [PMID: 24633564]
[http://dx.doi.org/10.1093/jat/23.2.86] [PMID: 10192410]
[http://dx.doi.org/10.1002/anie.201802082] [PMID: 29660223]
[http://dx.doi.org/10.1002/chem.201504248] [PMID: 26788864]
[http://dx.doi.org/10.1021/ma400093w]
[http://dx.doi.org/10.1002/chem.200600168] [PMID: 16847990]
[http://dx.doi.org/10.1081/SCC-100106048]
[http://dx.doi.org/10.1080/10426509808032465]
[http://dx.doi.org/10.1016/j.jfluchem.2005.08.017]
[http://dx.doi.org/10.1002/jlcr.699]
[http://dx.doi.org/10.1016/0022-328X(86)80314-X]
[http://dx.doi.org/10.1002/jlcr.2580250310]
[http://dx.doi.org/10.1021/ja00713a034]
[http://dx.doi.org/10.1021/jm050518j] [PMID: 16392809]
[http://dx.doi.org/10.1021/acs.orglett.5b00799] [PMID: 25970636]
[http://dx.doi.org/10.1055/s-0030-1258132]
[http://dx.doi.org/10.1002/(SICI)1096-9063(199803)52:3<263:AID-PS697>3.0.CO;2-8]
[http://dx.doi.org/10.1016/j.tetlet.2008.09.044]
[http://dx.doi.org/10.1016/j.tetlet.2005.06.024]
[http://dx.doi.org/10.1080/00304940509354988]
[http://dx.doi.org/10.1246/cl.2006.312]
[http://dx.doi.org/10.1080/00397919308011275]
[http://dx.doi.org/10.1080/10426500500543008]
[http://dx.doi.org/10.1016/S0040-4039(01)95485-1]
[http://dx.doi.org/10.1080/10643380701643650]
[http://dx.doi.org/10.1093/toxsci/kfq157] [PMID: 20498005]
[http://dx.doi.org/10.1111/nyas.13137] [PMID: 27467073]
[http://dx.doi.org/10.1093/toxsci/kfq356] [PMID: 21097996]
[http://dx.doi.org/10.1016/j.neuro.2015.11.014] [PMID: 26619911]
[http://dx.doi.org/10.1021/bi982678l] [PMID: 10353814]
[http://dx.doi.org/10.1016/j.cbi.2018.10.026] [PMID: 30389396]
[http://dx.doi.org/10.1124/jpet.117.247106] [PMID: 30115757]
[http://dx.doi.org/10.1016/j.bbi.2017.08.003] [PMID: 28782715]
[http://dx.doi.org/10.1002/jcb.20591] [PMID: 16149071]
[http://dx.doi.org/10.1007/s11010-005-9084-4] [PMID: 16924422]
[http://dx.doi.org/10.1016/j.bmc.2013.05.018] [PMID: 23769165]
[http://dx.doi.org/10.1016/j.neuro.2014.06.001] [PMID: 24928201]
[http://dx.doi.org/10.1007/s11064-015-1729-4] [PMID: 26438150]
[http://dx.doi.org/10.1002/etc.5620180221]
[http://dx.doi.org/10.1074/jbc.271.20.11953] [PMID: 8662593]
[http://dx.doi.org/10.1016/j.tetlet.2009.03.151]
[http://dx.doi.org/10.1016/j.tetlet.2005.02.026]
[http://dx.doi.org/10.1016/j.tetlet.2015.06.014]
[http://dx.doi.org/10.1080/00397910802215880]
[http://dx.doi.org/10.1016/j.jfluchem.2007.11.008]
[http://dx.doi.org/10.1155/2016/3190891]
[http://dx.doi.org/10.1016/j.tetlet.2008.02.051]
[http://dx.doi.org/10.1007/BF00960364]
[http://dx.doi.org/10.1070/MC1991v001n04ABEH000079]
[http://dx.doi.org/10.1139/v66-067]
[http://dx.doi.org/10.1039/c39870000755]
[http://dx.doi.org/10.1021/cr00044a004]
[http://dx.doi.org/10.1016/j.snb.2018.04.058]
[http://dx.doi.org/10.1016/j.talanta.2010.03.003] [PMID: 20441940]
[http://dx.doi.org/10.1016/j.cbi.2008.05.036] [PMID: 18588863]
[http://dx.doi.org/10.1002/chem.200800461] [PMID: 18454436]
[http://dx.doi.org/10.1002/jms.2038] [PMID: 22359323]
[http://dx.doi.org/10.1021/es049144u] [PMID: 15926571]
[http://dx.doi.org/10.1080/00032719708001688]
[http://dx.doi.org/10.1073/pnas.0401309101] [PMID: 15148405]
[http://dx.doi.org/10.1063/1.2166692]
[http://dx.doi.org/10.1117/12.579102]
[http://dx.doi.org/10.1016/j.tox.2015.12.001] [PMID: 26705700]
[http://dx.doi.org/10.1016/j.tox.2015.08.002] [PMID: 26275814]
[http://dx.doi.org/10.1021/tx900090m] [PMID: 19715348]
[http://dx.doi.org/10.1021/ac100176r] [PMID: 20384284]
[http://dx.doi.org/10.1002/anie.200902820] [PMID: 19757467]
[http://dx.doi.org/10.1021/tx900096j] [PMID: 19715346]
[http://dx.doi.org/10.1039/jr9520003437]
[http://dx.doi.org/10.1016/S0968-0896(01)00113-4] [PMID: 11504644]
[http://dx.doi.org/10.1016/j.tox.2006.09.020] [PMID: 17129656]
[http://dx.doi.org/10.1093/jat/32.1.86] [PMID: 18269799]
[PMID: 2917983]
[http://dx.doi.org/10.1021/bi00036a028] [PMID: 7547883]
[http://dx.doi.org/10.1021/bi9611220] [PMID: 8718893]
[http://dx.doi.org/10.1016/S0040-4039(01)83348-7]
[http://dx.doi.org/10.1039/p19790001646]
[http://dx.doi.org/10.1007/s11095-006-9123-1] [PMID: 17096183]
[http://dx.doi.org/10.1021/bi101763c] [PMID: 21332126]
[http://dx.doi.org/10.1080/15287394.2010.501716] [PMID: 21120745]
[http://dx.doi.org/10.1016/j.etap.2015.08.032] [PMID: 26462182]
[http://dx.doi.org/10.1021/acs.biochem.5b00199] [PMID: 25873441]
[http://dx.doi.org/10.1093/toxsci/kfu205] [PMID: 25304213]
[http://dx.doi.org/10.1021/bi5004266] [PMID: 24832101]
[http://dx.doi.org/10.1124/jpet.112.201368] [PMID: 23192655]
[http://dx.doi.org/10.1016/j.tox.2018.10.015] [PMID: 30359675]
[http://dx.doi.org/10.1021/acs.jmedchem.8b00592] [PMID: 30125110]
[http://dx.doi.org/10.1016/j.cbi.2012.10.017] [PMID: 23123249]
[http://dx.doi.org/10.1051/apido/2010018]
[http://dx.doi.org/10.1016/S0006-2952(98)00035-5] [PMID: 9744565]
[http://dx.doi.org/10.1080/09712119.2015.1031776]
[http://dx.doi.org/10.1016/j.ntt.2011.10.004] [PMID: 22036888]
[http://dx.doi.org/10.1016/S0147-6513(02)00013-1] [PMID: 12651185]
[http://dx.doi.org/10.1080/15376520500195566] [PMID: 20021025]
[http://dx.doi.org/10.5271/sjweh.380] [PMID: 10204668]
[http://dx.doi.org/10.1002/chem.201201039] [PMID: 22782929]
[http://dx.doi.org/10.1603/0022-0493-95.2.227] [PMID: 12019994]
[http://dx.doi.org/10.1080/03601230701310500] [PMID: 17474014]
[http://dx.doi.org/10.1021/jf010431g] [PMID: 11743808]
[http://dx.doi.org/10.1016/j.ejmech.2015.03.040] [PMID: 25812965]
[http://dx.doi.org/10.1016/j.tetlet.2006.03.030]
[http://dx.doi.org/10.3987/COM-07-11175]
[http://dx.doi.org/10.1016/j.bmc.2009.10.047] [PMID: 19932027]
[http://dx.doi.org/10.1021/acs.joc.5b01713] [PMID: 26509478]
[http://dx.doi.org/10.1021/jo202577m] [PMID: 22248005]
[http://dx.doi.org/10.1021/jacs.5b12081] [PMID: 26714650]
[http://dx.doi.org/10.1055/s-0036-1588941]
[http://dx.doi.org/10.1021/jacs.8b01561] [PMID: 29596743]
[http://dx.doi.org/10.1055/s-0031-1290344]
[http://dx.doi.org/10.1055/s-2005-865282]
[http://dx.doi.org/10.1016/S0040-4039(01)02041-X]
[http://dx.doi.org/10.1080/00397911.2014.926374]
[http://dx.doi.org/10.1016/j.bmc.2013.02.017] [PMID: 23517722]
[http://dx.doi.org/10.2174/1385272820666151026224227]
[http://dx.doi.org/10.3390/molecules23102417] [PMID: 30241375]
[http://dx.doi.org/10.1515/9783110535839-003]
[http://dx.doi.org/10.1080/14756360701632031] [PMID: 18608787]
[http://dx.doi.org/10.2174/1570159X11311030006] [PMID: 24179466]
[http://dx.doi.org/10.1111/j.1365-2672.2010.04672.x] [PMID: 20132373]
[http://dx.doi.org/10.1016/j.tox.2007.12.027] [PMID: 18294748]
[http://dx.doi.org/10.1016/j.tiv.2011.01.006] [PMID: 21238577]
[http://dx.doi.org/10.1016/j.bbrc.2014.04.155] [PMID: 24824182]
[http://dx.doi.org/10.1021/ac051052f] [PMID: 16383345]
[http://dx.doi.org/10.1021/bk-2001-0792.ch003]
[http://dx.doi.org/10.1016/S0009-2797(99)00056-3] [PMID: 10421481]
[http://dx.doi.org/10.1016/S0195-5616(90)50029-7] [PMID: 2180181]
[http://dx.doi.org/10.1067/mem.2003.103] [PMID: 12658242]
[http://dx.doi.org/10.1016/j.etap.2005.08.007] [PMID: 21783664]
[http://dx.doi.org/10.1007/978-1-4615-8491-9_6] [PMID: 4576326]
[http://dx.doi.org/10.1080/10937400701436445] [PMID: 18049927]
[http://dx.doi.org/10.1016/j.yrtph.2007.08.011] [PMID: 17936460]
[http://dx.doi.org/10.1002/ps.932] [PMID: 15578596]