On the intrinsic reactivity of highly potent trypanocidal cruzain inhibitors
The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Hence, peptidomimetic cruzipain inhibitors having a reactive group (known as warhead) are subject to continuous studies to discover novel antichagasic compounds. He...
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| Published in | MedChemComm Vol. 11; no. 11; pp. 1275 - 1284 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Cambridge
Royal Society of Chemistry
18.11.2020
RSC |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2632-8682 2040-2503 2632-8682 2040-2511 |
| DOI | 10.1039/d0md00097c |
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| Abstract | The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Hence, peptidomimetic cruzipain inhibitors having a reactive group (known as warhead) are subject to continuous studies to discover novel antichagasic compounds. Here, we evaluated how different warheads for a set of structurally similar related compounds could inhibit the activity of cruzipain and, ultimately, their trypanocidal effect. We first investigated
in silico
the intrinsic reactivity of these compounds by applying the Fukui index to correlate it with the enzymatic affinity. Then, we evaluated their potency against
T. cruzi
(Y and Tulahuen strains), which revealed the reversible cruzain inhibitor
Neq0656
as a better trypanocidal agent (EC
Y.strain
50
= 0.1 μM; SI = 58.4) than the current drug benznidazole (EC
Y.strain
50
= 5.1 μM; SI > 19.6). We also measured the half-life time by HPLC analysis of three lead compounds in the presence of glutathione and cysteine to experimentally assess their intrinsic reactivity. Results clearly illustrated the reactivity trend for the warheads (azanitrile > aldehyde > nitrile), where the aldehyde displayed an intermediate intrinsic reactivity. Therefore, the aldehyde bearing peptidomimetic compounds should be subject for in-depth evaluation in the drug discovery process.
Aldehyde peptide like compounds display a bivalent reactive profile and improved antichagasic potency. |
|---|---|
| AbstractList | The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Hence, peptidomimetic cruzipain inhibitors having a reactive group (known as warhead) are subject to continuous studies to discover novel antichagasic compounds. Here, we evaluated how different warheads for a set of structurally similar related compounds could inhibit the activity of cruzipain and, ultimately, their trypanocidal effect. We first investigated
in silico
the intrinsic reactivity of these compounds by applying the Fukui index to correlate it with the enzymatic affinity. Then, we evaluated their potency against
T. cruzi
(Y and Tulahuen strains), which revealed the reversible cruzain inhibitor
Neq0656
as a better trypanocidal agent (ECY.strain50 = 0.1 μM; SI = 58.4) than the current drug benznidazole (ECY.strain50 = 5.1 μM; SI > 19.6). We also measured the half-life time by HPLC analysis of three lead compounds in the presence of glutathione and cysteine to experimentally assess their intrinsic reactivity. Results clearly illustrated the reactivity trend for the warheads (azanitrile > aldehyde > nitrile), where the aldehyde displayed an intermediate intrinsic reactivity. Therefore, the aldehyde bearing peptidomimetic compounds should be subject for in-depth evaluation in the drug discovery process. The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Hence, peptidomimetic cruzipain inhibitors having a reactive group (known as warhead) are subject to continuous studies to discover novel antichagasic compounds. Here, we evaluated how different warheads for a set of structurally similar related compounds could inhibit the activity of cruzipain and, ultimately, their trypanocidal effect. We first investigated in silico the intrinsic reactivity of these compounds by applying the Fukui index to correlate it with the enzymatic affinity. Then, we evaluated their potency against T. cruzi (Y and Tulahuen strains), which revealed the reversible cruzain inhibitor Neq0656 as a better trypanocidal agent (EC Y.strain 50 = 0.1 μM; SI = 58.4) than the current drug benznidazole (EC Y.strain 50 = 5.1 μM; SI > 19.6). We also measured the half-life time by HPLC analysis of three lead compounds in the presence of glutathione and cysteine to experimentally assess their intrinsic reactivity. Results clearly illustrated the reactivity trend for the warheads (azanitrile > aldehyde > nitrile), where the aldehyde displayed an intermediate intrinsic reactivity. Therefore, the aldehyde bearing peptidomimetic compounds should be subject for in-depth evaluation in the drug discovery process. Aldehyde peptide like compounds display a bivalent reactive profile and improved antichagasic potency. The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Hence, peptidomimetic cruzipain inhibitors having a reactive group (known as warhead) are subject to continuous studies to discover novel antichagasic compounds. Here, we evaluated how different warheads for a set of structurally similar related compounds could inhibit the activity of cruzipain and, ultimately, their trypanocidal effect. We first investigated in silico the intrinsic reactivity of these compounds by applying the Fukui index to correlate it with the enzymatic affinity. Then, we evaluated their potency against T. cruzi (Y and Tulahuen strains), which revealed the reversible cruzain inhibitor Neq0656 as a better trypanocidal agent (EC50Y.strain = 0.1 μM; SI = 58.4) than the current drug benznidazole (EC50Y.strain = 5.1 μM; SI > 19.6). We also measured the half-life time by HPLC analysis of three lead compounds in the presence of glutathione and cysteine to experimentally assess their intrinsic reactivity. Results clearly illustrated the reactivity trend for the warheads (azanitrile > aldehyde > nitrile), where the aldehyde displayed an intermediate intrinsic reactivity. Therefore, the aldehyde bearing peptidomimetic compounds should be subject for in-depth evaluation in the drug discovery process. The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Hence, peptidomimetic cruzipain inhibitors having a reactive group (known as warhead) are subject to continuous studies to discover novel antichagasic compounds. Here, we evaluated how different warheads for a set of structurally similar related compounds could inhibit the activity of cruzipain and, ultimately, their trypanocidal effect. We first investigated in silico the intrinsic reactivity of these compounds by applying the Fukui index to correlate it with the enzymatic affinity. Then, we evaluated their potency against T. cruzi (Y and Tulahuen strains), which revealed the reversible cruzain inhibitor Neq0656 as a better trypanocidal agent (ECY.strain 50 = 0.1 μM; SI = 58.4) than the current drug benznidazole (ECY.strain 50 = 5.1 μM; SI > 19.6). We also measured the half-life time by HPLC analysis of three lead compounds in the presence of glutathione and cysteine to experimentally assess their intrinsic reactivity. Results clearly illustrated the reactivity trend for the warheads (azanitrile > aldehyde > nitrile), where the aldehyde displayed an intermediate intrinsic reactivity. Therefore, the aldehyde bearing peptidomimetic compounds should be subject for in-depth evaluation in the drug discovery process.The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Hence, peptidomimetic cruzipain inhibitors having a reactive group (known as warhead) are subject to continuous studies to discover novel antichagasic compounds. Here, we evaluated how different warheads for a set of structurally similar related compounds could inhibit the activity of cruzipain and, ultimately, their trypanocidal effect. We first investigated in silico the intrinsic reactivity of these compounds by applying the Fukui index to correlate it with the enzymatic affinity. Then, we evaluated their potency against T. cruzi (Y and Tulahuen strains), which revealed the reversible cruzain inhibitor Neq0656 as a better trypanocidal agent (ECY.strain 50 = 0.1 μM; SI = 58.4) than the current drug benznidazole (ECY.strain 50 = 5.1 μM; SI > 19.6). We also measured the half-life time by HPLC analysis of three lead compounds in the presence of glutathione and cysteine to experimentally assess their intrinsic reactivity. Results clearly illustrated the reactivity trend for the warheads (azanitrile > aldehyde > nitrile), where the aldehyde displayed an intermediate intrinsic reactivity. Therefore, the aldehyde bearing peptidomimetic compounds should be subject for in-depth evaluation in the drug discovery process. |
| Author | Tezuka, Daiane Y Moraes, Carolina Borsoi de Albuquerque, Sérgio Silva, Daniel G Batista, Pedro Henrique Jatai Cianni, Lorenzo Montanari, Carlos A Cedron, Rodrigo Leitão, Andrei Bonatto, Vinicius De Vita, Daniela Franco, Caio Haddad Lameira, Jerônimo |
| AuthorAffiliation | Centro Nacional de Pesquisa em Energia e Materiais (CNPEM) University of São Paulo Ribeirão Preto School of Pharmaceutical Sciences Universidade Federal do Pará Laboratório Nacional de Biociências (LNBio) Institute of Chemistry of São Carlos Instituto de Ciências Exatas e Naturais Medicinal Chemistry Group Laboratório de Planejamento e Desenvolvimento de Fármacos |
| AuthorAffiliation_xml | – name: Laboratório Nacional de Biociências (LNBio) – name: Ribeirão Preto School of Pharmaceutical Sciences – name: Instituto de Ciências Exatas e Naturais – name: Universidade Federal do Pará – name: University of São Paulo – name: Medicinal Chemistry Group – name: Institute of Chemistry of São Carlos – name: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM) – name: Laboratório de Planejamento e Desenvolvimento de Fármacos |
| Author_xml | – sequence: 1 givenname: Vinicius surname: Bonatto fullname: Bonatto, Vinicius – sequence: 2 givenname: Pedro Henrique Jatai surname: Batista fullname: Batista, Pedro Henrique Jatai – sequence: 3 givenname: Lorenzo surname: Cianni fullname: Cianni, Lorenzo – sequence: 4 givenname: Daniela surname: De Vita fullname: De Vita, Daniela – sequence: 5 givenname: Daniel G surname: Silva fullname: Silva, Daniel G – sequence: 6 givenname: Rodrigo surname: Cedron fullname: Cedron, Rodrigo – sequence: 7 givenname: Daiane Y surname: Tezuka fullname: Tezuka, Daiane Y – sequence: 8 givenname: Sérgio surname: de Albuquerque fullname: de Albuquerque, Sérgio – sequence: 9 givenname: Carolina Borsoi surname: Moraes fullname: Moraes, Carolina Borsoi – sequence: 10 givenname: Caio Haddad surname: Franco fullname: Franco, Caio Haddad – sequence: 11 givenname: Jerônimo surname: Lameira fullname: Lameira, Jerônimo – sequence: 12 givenname: Andrei surname: Leitão fullname: Leitão, Andrei – sequence: 13 givenname: Carlos A surname: Montanari fullname: Montanari, Carlos A |
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| Cites_doi | 10.1016/S0021-9258(19)77815-6 10.1186/1678-9199-19-34 10.1006/jmbi.1994.0137 10.1039/c2ob00034b 10.1021/ja00279a008 10.1177/1087057114550585 10.1021/acs.biochem.7b00271 10.1103/PhysRevB.37.785 10.1103/PhysRev.46.618 10.3109/03602532.2013.853078 10.1021/acs.jcim.7b00553 10.1016/j.bmc.2019.115083 10.1021/cr00088a005 10.1016/j.bmcl.2008.12.105 10.1021/ja9924039 10.1016/j.compbiolchem.2018.04.015 10.1021/jo00229a011 10.1016/0166-1280(88)80397-X 10.1063/1.464913 10.1021/acs.jcim.9b00316 10.1111/tmi.12235 10.1063/1.447079 10.1002/anie.200705858 10.1016/j.ejmech.2018.10.010 10.1016/j.bmcl.2017.10.002 10.1038/nature09221 10.1021/jm4004285 10.1021/acs.jcim.9b01138 10.1371/journal.pntd.0005343 10.1016/j.actatropica.2014.07.005 10.1063/1.473580 10.1016/j.bmc.2004.08.013 10.1021/acsmedchemlett.5b00336 10.1021/cr040109f 10.1590/0074-0276140156 10.1021/jo201465g 10.1016/j.saa.2017.07.036 10.1021/tx5001046 10.1039/C8CP03320J 10.1021/acs.jmedchem.8b01153 10.1016/0301-0104(81)85090-2 10.1021/jo030125x 10.1126/science.abb4489 10.1128/CMR.00005-11 10.1016/j.bmcl.2006.11.044 10.1371/journal.pntd.0003916 10.1016/j.bmc.2019.04.002 10.1021/acs.jmedchem.9b00683 10.1021/ct100684s 10.1016/j.bioorg.2018.04.006 10.1016/S0166-6851(01)00236-5 |
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| References | Cianni (D0MD00097C-(cit12)/*[position()=1]) 2019; 62 Löser (D0MD00097C-(cit49)/*[position()=1]) 2008; 47 Mondal Roy (D0MD00097C-(cit27)/*[position()=1]) 2018; 75 Lonsdale (D0MD00097C-(cit16)/*[position()=1]) 2017; 57 Pereira (D0MD00097C-(cit5)/*[position()=1]) 2013; 19 D0MD00097C-(cit13)/*[position()=1] Lima (D0MD00097C-(cit29)/*[position()=1]) 2001; 114 Cianni (D0MD00097C-(cit9)/*[position()=1]) 2018; 79 Chattaraj (D0MD00097C-(cit41)/*[position()=1]) 2006; 106 Pérez (D0MD00097C-(cit45)/*[position()=1]) 2003; 68 Yang (D0MD00097C-(cit46)/*[position()=1]) 1986; 108 Oballa (D0MD00097C-(cit25)/*[position()=1]) 2007; 17 Wriede (D0MD00097C-(cit48)/*[position()=1]) 1987; 52 Chatelain (D0MD00097C-(cit3)/*[position()=1]) 2015; 20 Gonzalez-Suarez (D0MD00097C-(cit22)/*[position()=1]) 2012; 77 Gehringer (D0MD00097C-(cit15)/*[position()=1]) 2019; 62 Bern (D0MD00097C-(cit2)/*[position()=1]) 2011; 24 Silva (D0MD00097C-(cit32)/*[position()=1]) 2020; 60 Frisch (D0MD00097C-(cit38)/*[position()=1]) 1984; 80 Miertuš (D0MD00097C-(cit40)/*[position()=1]) 1981; 55 Lee (D0MD00097C-(cit43)/*[position()=1]) 1988; 163 Ábrányi-Balogh (D0MD00097C-(cit18)/*[position()=1]) 2018; 160 Parthasarathi (D0MD00097C-(cit28)/*[position()=1]) 2004; 12 Martin (D0MD00097C-(cit19)/*[position()=1]) 2019; 27 Ehmke (D0MD00097C-(cit24)/*[position()=1]) 2012; 10 Møller (D0MD00097C-(cit39)/*[position()=1]) 1934; 46 McGrath (D0MD00097C-(cit6)/*[position()=1]) 1995; 247 McGregor (D0MD00097C-(cit20)/*[position()=1]) 2017; 56 Palazzesi (D0MD00097C-(cit23)/*[position()=1]) 2019; 59 LoPachin (D0MD00097C-(cit50)/*[position()=1]) 2014; 27 Lee (D0MD00097C-(cit37)/*[position()=1]) 1988; 37 Reed (D0MD00097C-(cit47)/*[position()=1]) 1988; 88 Malátková (D0MD00097C-(cit52)/*[position()=1]) 2014; 46 Meister (D0MD00097C-(cit33)/*[position()=1]) 1988; 263 Rodriguez (D0MD00097C-(cit31)/*[position()=1]) 2014; 139 Burtoloso (D0MD00097C-(cit8)/*[position()=1]) 2017; 11 Zingales (D0MD00097C-(cit30)/*[position()=1]) 2014; 109 Gaus (D0MD00097C-(cit35)/*[position()=1]) 2011; 7 Liu (D0MD00097C-(cit44)/*[position()=1]) 1997; 106 Jackson (D0MD00097C-(cit4)/*[position()=1]) 2014; 19 Jones (D0MD00097C-(cit14)/*[position()=1]) 2016; 7 Dos Santos (D0MD00097C-(cit34)/*[position()=1]) 2018; 20 MacFaul (D0MD00097C-(cit17)/*[position()=1]) 2009; 19 Gomes (D0MD00097C-(cit10)/*[position()=1]) 2019; 27 Coura (D0MD00097C-(cit1)/*[position()=1]) 2010; 465 Ayers (D0MD00097C-(cit42)/*[position()=1]) 2000; 122 Avelar (D0MD00097C-(cit7)/*[position()=1]) 2015; 9 Sayin (D0MD00097C-(cit21)/*[position()=1]) 2018; 188 Dai (D0MD00097C-(cit51)/*[position()=1]) 2020; 368 Silva (D0MD00097C-(cit11)/*[position()=1]) 2017; 27 Becke (D0MD00097C-(cit36)/*[position()=1]) 1993; 98 Cherkasov (D0MD00097C-(cit26)/*[position()=1]) 2014; 57 |
| References_xml | – volume: 263 start-page: 17205 year: 1988 ident: D0MD00097C-(cit33)/*[position()=1] publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(19)77815-6 – volume: 19 start-page: 34 year: 2013 ident: D0MD00097C-(cit5)/*[position()=1] publication-title: J. Venomous Anim. Toxins Incl. Trop. Dis. doi: 10.1186/1678-9199-19-34 – volume: 247 start-page: 251 year: 1995 ident: D0MD00097C-(cit6)/*[position()=1] publication-title: J. Mol. Biol. doi: 10.1006/jmbi.1994.0137 – volume: 10 start-page: 5764 year: 2012 ident: D0MD00097C-(cit24)/*[position()=1] publication-title: Org. Biomol. Chem. doi: 10.1039/c2ob00034b – volume: 108 start-page: 5708 year: 1986 ident: D0MD00097C-(cit46)/*[position()=1] publication-title: J. Am. Chem. Soc. doi: 10.1021/ja00279a008 – volume: 20 start-page: 22 year: 2015 ident: D0MD00097C-(cit3)/*[position()=1] publication-title: J. Biomol. Screening doi: 10.1177/1087057114550585 – volume: 56 start-page: 3178 year: 2017 ident: D0MD00097C-(cit20)/*[position()=1] publication-title: Biochemistry doi: 10.1021/acs.biochem.7b00271 – volume: 37 start-page: 785 year: 1988 ident: D0MD00097C-(cit37)/*[position()=1] publication-title: Phys. Rev. B: Condens. Matter Mater. Phys. doi: 10.1103/PhysRevB.37.785 – volume: 46 start-page: 618 year: 1934 ident: D0MD00097C-(cit39)/*[position()=1] publication-title: Phys. Rev. doi: 10.1103/PhysRev.46.618 – volume: 46 start-page: 96 year: 2014 ident: D0MD00097C-(cit52)/*[position()=1] publication-title: Drug Metab. Rev. doi: 10.3109/03602532.2013.853078 – volume: 57 start-page: 3124 year: 2017 ident: D0MD00097C-(cit16)/*[position()=1] publication-title: J. Chem. Inf. Model. doi: 10.1021/acs.jcim.7b00553 – volume: 27 start-page: 115083 year: 2019 ident: D0MD00097C-(cit10)/*[position()=1] publication-title: Bioorg. Med. Chem. doi: 10.1016/j.bmc.2019.115083 – volume: 88 start-page: 899 year: 1988 ident: D0MD00097C-(cit47)/*[position()=1] publication-title: Chem. Rev. doi: 10.1021/cr00088a005 – volume: 19 start-page: 1136 year: 2009 ident: D0MD00097C-(cit17)/*[position()=1] publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/j.bmcl.2008.12.105 – volume: 122 start-page: 2010 year: 2000 ident: D0MD00097C-(cit42)/*[position()=1] publication-title: J. Am. Chem. Soc. doi: 10.1021/ja9924039 – volume: 75 start-page: 91 year: 2018 ident: D0MD00097C-(cit27)/*[position()=1] publication-title: Comput. Biol. Chem. doi: 10.1016/j.compbiolchem.2018.04.015 – volume: 52 start-page: 4485 year: 1987 ident: D0MD00097C-(cit48)/*[position()=1] publication-title: J. Org. Chem. doi: 10.1021/jo00229a011 – volume: 163 start-page: 305 year: 1988 ident: D0MD00097C-(cit43)/*[position()=1] publication-title: J. Mol. Struct.: THEOCHEM doi: 10.1016/0166-1280(88)80397-X – volume: 98 start-page: 5648 year: 1993 ident: D0MD00097C-(cit36)/*[position()=1] publication-title: J. Chem. Phys. doi: 10.1063/1.464913 – volume: 59 start-page: 3565 year: 2019 ident: D0MD00097C-(cit23)/*[position()=1] publication-title: J. Chem. Inf. Model. doi: 10.1021/acs.jcim.9b00316 – volume: 19 start-page: 212 year: 2014 ident: D0MD00097C-(cit4)/*[position()=1] publication-title: Trop. Med. Int. Health doi: 10.1111/tmi.12235 – volume: 80 start-page: 3265 year: 1984 ident: D0MD00097C-(cit38)/*[position()=1] publication-title: J. Chem. Phys. doi: 10.1063/1.447079 – volume: 47 start-page: 4331 year: 2008 ident: D0MD00097C-(cit49)/*[position()=1] publication-title: Angew. Chem., Int. Ed. doi: 10.1002/anie.200705858 – volume: 160 start-page: 94 year: 2018 ident: D0MD00097C-(cit18)/*[position()=1] publication-title: Eur. J. Med. Chem. doi: 10.1016/j.ejmech.2018.10.010 – volume: 27 start-page: 5031 year: 2017 ident: D0MD00097C-(cit11)/*[position()=1] publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/j.bmcl.2017.10.002 – volume: 465 start-page: S6 year: 2010 ident: D0MD00097C-(cit1)/*[position()=1] publication-title: Nature doi: 10.1038/nature09221 – volume: 57 start-page: 4977 year: 2014 ident: D0MD00097C-(cit26)/*[position()=1] publication-title: J. Med. Chem. doi: 10.1021/jm4004285 – volume: 60 start-page: 1666 year: 2020 ident: D0MD00097C-(cit32)/*[position()=1] publication-title: J. Chem. Inf. Model. doi: 10.1021/acs.jcim.9b01138 – ident: D0MD00097C-(cit13)/*[position()=1] – volume: 11 start-page: e0005343 year: 2017 ident: D0MD00097C-(cit8)/*[position()=1] publication-title: PLoS Neglected Trop. Dis. doi: 10.1371/journal.pntd.0005343 – volume: 139 start-page: 57 year: 2014 ident: D0MD00097C-(cit31)/*[position()=1] publication-title: Acta Trop. doi: 10.1016/j.actatropica.2014.07.005 – volume: 106 start-page: 5578 year: 1997 ident: D0MD00097C-(cit44)/*[position()=1] publication-title: J. Chem. Phys. doi: 10.1063/1.473580 – volume: 12 start-page: 5533 year: 2004 ident: D0MD00097C-(cit28)/*[position()=1] publication-title: Bioorg. Med. Chem. doi: 10.1016/j.bmc.2004.08.013 – volume: 7 start-page: 77 year: 2016 ident: D0MD00097C-(cit14)/*[position()=1] publication-title: ACS Med. Chem. Lett. doi: 10.1021/acsmedchemlett.5b00336 – volume: 106 start-page: 2065 year: 2006 ident: D0MD00097C-(cit41)/*[position()=1] publication-title: Chem. Rev. doi: 10.1021/cr040109f – volume: 109 start-page: 828 year: 2014 ident: D0MD00097C-(cit30)/*[position()=1] publication-title: Mem. Inst. Oswaldo Cruz doi: 10.1590/0074-0276140156 – volume: 77 start-page: 90 year: 2012 ident: D0MD00097C-(cit22)/*[position()=1] publication-title: J. Org. Chem. doi: 10.1021/jo201465g – volume: 188 start-page: 537 year: 2018 ident: D0MD00097C-(cit21)/*[position()=1] publication-title: Spectrochim. Acta, Part A doi: 10.1016/j.saa.2017.07.036 – volume: 27 start-page: 1081 year: 2014 ident: D0MD00097C-(cit50)/*[position()=1] publication-title: Chem. Res. Toxicol. doi: 10.1021/tx5001046 – volume: 20 start-page: 24317 year: 2018 ident: D0MD00097C-(cit34)/*[position()=1] publication-title: Phys. Chem. Chem. Phys. doi: 10.1039/C8CP03320J – volume: 62 start-page: 5673 year: 2019 ident: D0MD00097C-(cit15)/*[position()=1] publication-title: J. Med. Chem. doi: 10.1021/acs.jmedchem.8b01153 – volume: 55 start-page: 117 year: 1981 ident: D0MD00097C-(cit40)/*[position()=1] publication-title: Chem. Phys. doi: 10.1016/0301-0104(81)85090-2 – volume: 68 start-page: 5886 year: 2003 ident: D0MD00097C-(cit45)/*[position()=1] publication-title: J. Org. Chem. doi: 10.1021/jo030125x – volume: 368 start-page: 1331 year: 2020 ident: D0MD00097C-(cit51)/*[position()=1] publication-title: Science doi: 10.1126/science.abb4489 – volume: 24 start-page: 655 year: 2011 ident: D0MD00097C-(cit2)/*[position()=1] publication-title: Clin. Microbiol. Rev. doi: 10.1128/CMR.00005-11 – volume: 17 start-page: 998 year: 2007 ident: D0MD00097C-(cit25)/*[position()=1] publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/j.bmcl.2006.11.044 – volume: 9 start-page: e0003916 year: 2015 ident: D0MD00097C-(cit7)/*[position()=1] publication-title: PLoS Neglected Trop. Dis. doi: 10.1371/journal.pntd.0003916 – volume: 27 start-page: 2066 year: 2019 ident: D0MD00097C-(cit19)/*[position()=1] publication-title: Bioorg. Med. Chem. doi: 10.1016/j.bmc.2019.04.002 – volume: 62 start-page: 10497 year: 2019 ident: D0MD00097C-(cit12)/*[position()=1] publication-title: J. Med. Chem. doi: 10.1021/acs.jmedchem.9b00683 – volume: 7 start-page: 931 year: 2011 ident: D0MD00097C-(cit35)/*[position()=1] publication-title: J. Chem. Theory Comput. doi: 10.1021/ct100684s – volume: 79 start-page: 285 year: 2018 ident: D0MD00097C-(cit9)/*[position()=1] publication-title: Bioorg. Chem. doi: 10.1016/j.bioorg.2018.04.006 – volume: 114 start-page: 41 year: 2001 ident: D0MD00097C-(cit29)/*[position()=1] publication-title: Mol. Biochem. Parasitol. doi: 10.1016/S0166-6851(01)00236-5 |
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| SubjectTerms | Aldehydes Benznidazole Chagas disease Chemistry Cruzipain Cysteine Cysteine proteinase Evaluation Glutathione High-performance liquid chromatography Inhibitors Lead compounds Liquid chromatography Reactivity Vector-borne diseases Warheads |
| Title | On the intrinsic reactivity of highly potent trypanocidal cruzain inhibitors |
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