{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:12:47Z","timestamp":1788459167135,"version":"build-2803163510"},"reference-count":75,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:00:00Z","timestamp":1607558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccby_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1171488"],"award-info":[{"award-number":["OPP1171488"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","award":["Gilead Sciences & IOCB Research Center"],"award-info":[{"award-number":["Gilead Sciences & IOCB Research Center"]}],"id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI126296"],"award-info":[{"award-number":["R21AI126296"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["PROGRES Q25"],"award-info":[{"award-number":["PROGRES Q25"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a Telov\u00fdchovy","doi-asserted-by":"publisher","award":["LM2015070"],"award-info":[{"award-number":["LM2015070"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a Telov\u00fdchovy","doi-asserted-by":"publisher","award":["LTAUSA19109"],"award-info":[{"award-number":["LTAUSA19109"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a Telov\u00fdchovy","doi-asserted-by":"publisher","award":["RVO 61388963"],"award-info":[{"award-number":["RVO 61388963"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["NV18-05-00345"],"award-info":[{"award-number":["NV18-05-00345"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["ChemBioDrug CZ.02.1.01\/0.0\/0.0\/16_019\/0000729"],"award-info":[{"award-number":["ChemBioDrug CZ.02.1.01\/0.0\/0.0\/16_019\/0000729"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Azapeptide nitriles are postulated to reversibly covalently react with the active-site cysteine residue of cysteine proteases and form isothiosemicarbazide adducts. We investigated the interaction of azadipeptide nitriles with the cathepsin B1 drug target (SmCB1) from Schistosoma mansoni, a pathogen that causes the global neglected disease schistosomiasis. Azadipeptide nitriles were superior inhibitors of SmCB1 over their parent carba analogs. We determined the crystal structure of SmCB1 in complex with an azadipeptide nitrile and analyzed the reaction mechanism using quantum chemical calculations. The data demonstrate that azadipeptide nitriles, in contrast to their carba counterparts, undergo a change from E- to Z-configuration upon binding, which gives rise to a highly favorable energy profile of noncovalent and covalent complex formation. Finally, azadipeptide nitriles were considerably more lethal than their carba analogs against the schistosome pathogen in culture, supporting the further development of this chemotype as a treatment for schistosomiasis.<\/jats:p>","DOI":"10.1021\/acsinfecdis.0c00644","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T02:55:35Z","timestamp":1607655335000},"page":"189-201","source":"Crossref","is-referenced-by-count":23,"title":["Azanitrile Inhibitors of the SmCB1 Protease Target\nAre Lethal to\n                    <i>Schistosoma mansoni<\/i>\n                    : Structural and\nMechanistic Insights into Chemotype Reactivity"],"prefix":"10.1021","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0847-5022","authenticated-orcid":true,"given":"Ade\u0301la","family":"Ji\u0301lkova\u0301","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences , Flemingovo n. 2 , ,","place":["Prague 6, Czech Republic, 16610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9110-2018","authenticated-orcid":true,"given":"Martin","family":"Horn","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences , Flemingovo n. 2 , ,","place":["Prague 6, Czech Republic, 16610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jindr\u030cich","family":"Fanfrli\u0301k","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences , Flemingovo n. 2 , ,","place":["Prague 6, Czech Republic, 16610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Ku\u0308ppers","sequence":"additional","affiliation":[{"name":"University of Bonn , , An der Immenburg 4 , ,","place":["Bonn, Germany, 53121"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Pachl","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences , Flemingovo n. 2 , ,","place":["Prague 6, Czech Republic, 16610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavli\u0301na","family":"R\u030ceza\u0301c\u030cova\u0301","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences , Flemingovo n. 2 , ,","place":["Prague 6, Czech Republic, 16610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2607-8132","authenticated-orcid":true,"given":"Martin","family":"Leps\u030ci\u0301k","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences , Flemingovo n. 2 , ,","place":["Prague 6, Czech Republic, 16610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavla","family":"Fajtova\u0301","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences , Flemingovo n. 2 , ,","place":["Prague 6, Czech Republic, 16610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Rubes\u030cova\u0301","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences , Flemingovo n. 2 , ,","place":["Prague 6, Czech Republic, 16610"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Chanova\u0301","sequence":"additional","affiliation":[{"name":"Charles University and General University Hospital in Prague , , Studnic\u030ckova 2028\/7 , ,","place":["Prague 2, Czech Republic, 12800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor R.","family":"Caffrey","sequence":"additional","affiliation":[{"name":"University of California San Diego , , 9500 Gilman Drive , , ,","place":["La Jolla, California, United States, 92093"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9376-7897","authenticated-orcid":true,"given":"Michael","family":"Gu\u0308tschow","sequence":"additional","affiliation":[{"name":"University of Bonn , , An der Immenburg 4 , ,","place":["Bonn, Germany, 53121"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mares\u030c","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences , Flemingovo n. 2 , ,","place":["Prague 6, Czech Republic, 16610"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,12,10]]},"reference":[{"issue":"7","key":"2026090313174045700_cit1","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1021\/acs.accounts.7b00114","article-title":"Azapeptide Synthesis Methods for\nExpanding Side-Chain Diversity for Biomedical Applications","volume":"50","author":"Chingle","year":"2017","journal-title":"Acc. Chem. Res."},{"issue":"9","key":"2026090313174045700_cit2","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.4155\/fmc.11.74","article-title":"Azapeptides and\ntheir therapeutic potential","volume":"3","author":"Proulx","year":"2011","journal-title":"Future Med. Chem."},{"issue":"6","key":"2026090313174045700_cit3","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1002\/cbic.200600001","article-title":"Novel aza\npeptide inhibitors and active-site probes of papain-family cysteine\nproteases","volume":"7","author":"Verhelst","year":"2006","journal-title":"ChemBioChem"},{"issue":"9","key":"2026090313174045700_cit4","doi-asserted-by":"publisher","first-page":"4500","DOI":"10.1021\/acs.jmedchem.9b00056","article-title":"Paired\nUtility of Aza-Amino Acyl\nProline and Indolizidinone Amino Acid Residues for Peptide Mimicry:\nConception of Prostaglandin F2alpha Receptor Allosteric Modulators\nThat Delay Preterm Birth","volume":"62","author":"Mir","year":"2019","journal-title":"J. Med. Chem."},{"issue":"4","key":"2026090313174045700_cit5","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/sj.cdd.4402074","article-title":"Specificity of aza-peptide electrophile activity-based probes of\ncaspases","volume":"14","author":"Sexton","year":"2007","journal-title":"Cell Death Differ."},{"issue":"23","key":"2026090313174045700_cit6","doi-asserted-by":"publisher","first-page":"4331","DOI":"10.1002\/anie.200705858","article-title":"Azadipeptide\nnitriles: highly potent and proteolytically stable inhibitors of papain-like\ncysteine proteases","volume":"47","author":"Lo\u0308ser","year":"2008","journal-title":"Angew. Chem., Int. Ed."},{"issue":"1","key":"2026090313174045700_cit7","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1021\/jm101272p","article-title":"Structural optimization of azadipeptide nitriles strongly\nincreases association rates and allows the development of selective\ncathepsin inhibitors","volume":"54","author":"Frizler","year":"2011","journal-title":"J. Med. Chem."},{"issue":"41","key":"2026090313174045700_cit8","doi-asserted-by":"publisher","first-page":"11419","DOI":"10.1002\/chem.201101350","article-title":"Facing the\ngem-dialkyl effect in enzyme inhibitor design: preparation of homocycloleucine-based\nazadipeptide nitriles","volume":"17","author":"Frizler","year":"2011","journal-title":"Chem. - Eur. J."},{"issue":"12","key":"2026090313174045700_cit9","doi-asserted-by":"publisher","first-page":"5982","DOI":"10.1021\/jm300734k","article-title":"Selective\nnitrile inhibitors to modulate the proteolytic synergism of cathepsins\nS and F","volume":"55","author":"Frizler","year":"2012","journal-title":"J. Med. Chem."},{"issue":"21","key":"2026090313174045700_cit10","doi-asserted-by":"publisher","first-page":"6528","DOI":"10.1002\/chem.201103322","article-title":"Design, synthesis and biological\nevaluation of potent\nazadipeptide nitrile inhibitors and activity-based probes as promising\nanti-Trypanosoma brucei agents","volume":"18","author":"Yang","year":"2012","journal-title":"Chem. - Eur. J."},{"issue":"44","key":"2026090313174045700_cit11","doi-asserted-by":"publisher","first-page":"8407","DOI":"10.1039\/c0cc03738a","article-title":"Click\u201d synthesis of small\nmolecule-peptide conjugates for organelle-specific delivery and inhibition\nof lysosomal cysteine proteases","volume":"46","author":"Loh","year":"2010","journal-title":"Chem. Commun.\n(Cambridge, U. K.)"},{"issue":"8","key":"2026090313174045700_cit12","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1002\/cmdc.201300135","article-title":"Synthesis and radiopharmacological characterisation\nof a fluorine-18-labelled azadipeptide nitrile as a potential PET\ntracer for in vivo imaging of cysteine cathepsins","volume":"8","author":"Lo\u0308ser","year":"2013","journal-title":"ChemMedChem"},{"key":"2026090313174045700_cit13","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/978-1-4939-6850-3_19","article-title":"Synthesis and\nApplication of Activity-Based Probes for Proteases","volume":"1574","author":"Van Kersavond","year":"2017","journal-title":"Methods Mol. Biol."},{"issue":"1","key":"2026090313174045700_cit14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227341","article-title":"Novel broad-spectrum\nactivity-based probes to profile malarial cysteine proteases","volume":"15","author":"Tan","year":"2020","journal-title":"PLoS One"},{"issue":"16","key":"2026090313174045700_cit15","doi-asserted-by":"publisher","first-page":"2604","DOI":"10.1111\/febs.14130","article-title":"Proteases\nas antimalarial targets: strategies for genetic, chemical, and therapeutic\nvalidation","volume":"284","author":"Deu","year":"2017","journal-title":"FEBS J."},{"issue":"20","key":"2026090313174045700_cit16","doi-asserted-by":"publisher","first-page":"9026","DOI":"10.1021\/acs.jmedchem.9b00294","article-title":"Design of Gallinamide\nA Analogs as\nPotent Inhibitors of the Cysteine Proteases Human Cathepsin L and Trypanosoma cruzi Cruzain","volume":"62","author":"Boudreau","year":"2019","journal-title":"J. Med.\nChem."},{"issue":"23","key":"2026090313174045700_cit17","doi-asserted-by":"publisher","first-page":"10617","DOI":"10.1021\/acs.jmedchem.9b00908","article-title":"Optimization\nStrategy of Novel Peptide-Based Michael Acceptors for the Treatment\nof Human African Trypanosomiasis","volume":"62","author":"Ettari","year":"2019","journal-title":"J. Med. Chem."},{"key":"2026090313174045700_cit18","doi-asserted-by":"publisher","DOI":"10.2174\/0929867327666200730215316","article-title":"Falcipain-2 and falcipain-3 inhibitors as promising antimalarial\nagents","author":"Ettari","year":"2020","journal-title":"Curr. Med. Chem."},{"issue":"1","key":"2026090313174045700_cit19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S0166-6851(03)00194-4","article-title":"Functional\nexpression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl\nendopeptidase","volume":"131","author":"Sajid","year":"2003","journal-title":"Mol. Biochem. Parasitol."},{"issue":"41","key":"2026090313174045700_cit20","doi-asserted-by":"publisher","first-page":"35770","DOI":"10.1074\/jbc.M111.271304","article-title":"Structural\nBasis for Inhibition of Cathepsin B Drug Target from the Human Blood\nFluke, Schistosoma mansoni","volume":"286","author":"Ji\u0301lkova\u0301","year":"2011","journal-title":"J. Biol. Chem."},{"issue":"9936","key":"2026090313174045700_cit21","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis","volume":"383","author":"Colley","year":"2014","journal-title":"Lancet"},{"issue":"4","key":"2026090313174045700_cit22","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.cbpa.2007.05.031","article-title":"Chemotherapy\nof schistosomiasis: present and future","volume":"11","author":"Caffrey","year":"2007","journal-title":"Curr.\nOpin. Chem. Biol."},{"issue":"5","key":"2026090313174045700_cit23","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1097\/QCO.0b013e328349156f","article-title":"Schistosomiasis: from drug deployment\nto drug development","volume":"24","author":"Caffrey","year":"2011","journal-title":"Curr. Opin. Infect. Dis."},{"issue":"31","key":"2026090313174045700_cit24","doi-asserted-by":"publisher","first-page":"7936","DOI":"10.1002\/anie.201208390","article-title":"Schistosomiasis chemotherapy","volume":"52","author":"Thetiot-Laurent","year":"2013","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090313174045700_cit25","doi-asserted-by":"crossref","DOI":"10.1002\/9783527808656.ch8","article-title":"Drug Discovery\nand Development for Schistosomiasis","volume-title":"Neglected\nTropical Diseases","author":"Caffrey","year":"2019"},{"issue":"1","key":"2026090313174045700_cit26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040014","article-title":"Schistosomiasis\nmansoni: novel chemotherapy using a cysteine protease inhibitor","volume":"4","author":"Abdulla","year":"2007","journal-title":"PLoS Med."},{"issue":"6","key":"2026090313174045700_cit27","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1021\/cb100411v","article-title":"Mapping the\nPro-Peptide of the Schistosoma mansoni Cathepsin\nB1 Drug Target: Modulation of Inhibition by Heparin and Design of\nMimetic Inhibitors","volume":"6","author":"Horn","year":"2011","journal-title":"ACS Chem. Biol."},{"issue":"12","key":"2026090313174045700_cit28","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1016\/j.str.2014.09.015","article-title":"Activation\nRoute of the Schistosoma mansoni Cathepsin B1 Drug\nTarget: Structural Map with a Glycosaminoglycan\nSwitch","volume":"22","author":"Ji\u0301lkova\u0301","year":"2014","journal-title":"Structure"},{"issue":"2","key":"2026090313174045700_cit29","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S0006-291X(67)80055-X","article-title":"On the size of the\nactive site in proteases. I. Papain","volume":"27","author":"Schechter","year":"1967","journal-title":"Biochem.\nBiophys. Res. Commun."},{"issue":"1","key":"2026090313174045700_cit30","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1021\/jm00151a018","article-title":"Carboxyl-modified\namino acids and\npeptides as protease inhibitors","volume":"29","author":"Thompson","year":"1986","journal-title":"J. Med. Chem."},{"issue":"1","key":"2026090313174045700_cit31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bmc.2018.10.017","article-title":"Cathepsin B: Active site mapping with peptidic substrates\nand inhibitors","volume":"27","author":"Schmitz","year":"2019","journal-title":"Bioorg. Med. Chem."},{"issue":"26","key":"2026090313174045700_cit32","doi-asserted-by":"publisher","first-page":"4524","DOI":"10.1021\/jm010206q","article-title":"Identification\nof dipeptidyl nitriles as potent and selective inhibitors of cathepsin\nB through structure-based drug design","volume":"44","author":"Greenspan","year":"2001","journal-title":"J. Med.\nChem."},{"issue":"46","key":"2026090313174045700_cit33","doi-asserted-by":"publisher","first-page":"5772","DOI":"10.1039\/c2cc31161e","article-title":"Induction of chirality: experimental\nevidence of atropisomerism in azapeptides","volume":"48","author":"Ottersbach","year":"2012","journal-title":"Chem.\nCommun. (Cambridge, U. K.)"},{"issue":"3","key":"2026090313174045700_cit34","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1021\/ol3030583","article-title":"An access\nto aza-Freidinger lactams and E-locked analogs","volume":"15","author":"Ottersbach","year":"2013","journal-title":"Org. Lett."},{"issue":"48","key":"2026090313174045700_cit35","doi-asserted-by":"publisher","first-page":"14973","DOI":"10.1021\/jp409604n","article-title":"Quantum Mechanics-Based\nScoring Rationalizes the Irreversible Inactivation of Parasitic Schistosoma mansoni Cysteine Peptidase by Vinyl Sulfone\nInhibitors","volume":"117","author":"Fanfrli\u0301k","year":"2013","journal-title":"J. Phys. Chem. B"},{"issue":"27","key":"2026090313174045700_cit36","doi-asserted-by":"publisher","first-page":"8696","DOI":"10.1021\/ja711043x","article-title":"On the origin of the stabilization\nof the zwitterionic\nresting state of cysteine proteases: a theoretical study","volume":"130","author":"Mladenovic","year":"2008","journal-title":"J. Am. Chem. Soc."},{"issue":"3","key":"2026090313174045700_cit37","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1021\/ct301082y","article-title":"Benchmark Study for the Cysteine-Histidine\nProton Transfer Reaction in a Protein Environment: Gas Phase, COSMO,\nQM\/MM Approaches","volume":"9","author":"Paasche","year":"2013","journal-title":"J. Chem. Theory Comput."},{"issue":"27","key":"2026090313174045700_cit38","doi-asserted-by":"publisher","first-page":"8332","DOI":"10.1021\/jacs.6b03052","article-title":"Quantum Chemical-Based\nProtocol for\nthe Rational Design of Covalent Inhibitors","volume":"138","author":"Schirmeister","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"2026090313174045700_cit39","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3389\/fchem.2013.00039","article-title":"Cysteine protease inhibition by nitrile-based\ninhibitors: a computational study","volume":"1","author":"Quesne","year":"2013","journal-title":"Front. Chem."},{"issue":"10","key":"2026090313174045700_cit40","doi-asserted-by":"publisher","first-page":"290","DOI":"10.3390\/cryst7100290","article-title":"Synthesis and X-ray Crystal Structure\nof N\u2019-Cyano-N,N\u2019-dimethyl-4-nitrobenzohydrazide","volume":"7","author":"Lo\u0308ser","year":"2017","journal-title":"Crystals"},{"issue":"4","key":"2026090313174045700_cit41","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1002\/ejoc.200300416","article-title":"N-acylhydrazines: Future perspectives offered by new\nsyntheses and chemistry","volume":"2004","author":"Licandro","year":"2004","journal-title":"Eur. J. Org. Chem."},{"issue":"30","key":"2026090313174045700_cit42","doi-asserted-by":"publisher","first-page":"5894","DOI":"10.1021\/bi3006913","article-title":"Conformational selection or induced fit? A critical\nappraisal of the kinetic mechanism","volume":"51","author":"Vogt","year":"2012","journal-title":"Biochemistry"},{"key":"2026090313174045700_cit43","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/9781118540398.ch6","article-title":"Slow Binding Inhibitors","volume-title":"Evaluation of\nEnzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists\nand Pharmacologists","author":"Copeland","year":"2013"},{"issue":"1","key":"2026090313174045700_cit44","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1021\/np400727r","article-title":"The marine cyanobacterial\nmetabolite\ngallinamide A is a potent and selective inhibitor of human cathepsin\nL","volume":"77","author":"Miller","year":"2014","journal-title":"J. Nat. Prod."},{"issue":"3","key":"2026090313174045700_cit45","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1002\/prot.22939","article-title":"The mechanism\nof papain inhibition\nby peptidyl aldehydes","volume":"79","author":"Shokhen","year":"2011","journal-title":"Proteins: Struct., Funct.,\nGenet."},{"issue":"23","key":"2026090313174045700_cit46","doi-asserted-by":"publisher","first-page":"8508","DOI":"10.1021\/bi9803325","article-title":"Bimodal\ninhibition of caspase-1 by aryloxymethyl and acyloxymethyl ketones","volume":"37","author":"Brady","year":"1998","journal-title":"Biochemistry"},{"issue":"8","key":"2026090313174045700_cit47","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1002\/jlcr.3729","article-title":"Synthesis\nand preliminary radiopharmacological\ncharacterisation of an 11C-labelled azadipeptide nitrile\nas potential PET tracer for imaging of cysteine cathepsins","volume":"62","author":"Laube","year":"2019","journal-title":"J. Labelled Compd. Radiopharm."},{"issue":"7","key":"2026090313174045700_cit48","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1021\/jm901137j","article-title":"New substructure\nfilters for removal of pan assay interference\ncompounds (PAINS) from screening libraries and for their exclusion\nin bioassays","volume":"53","author":"Baell","year":"2010","journal-title":"J. Med. Chem."},{"issue":"24","key":"2026090313174045700_cit49","doi-asserted-by":"publisher","first-page":"7688","DOI":"10.1021\/jm050686b","article-title":"Interaction\nof papain-like cysteine proteases with dipeptide-derived nitriles","volume":"48","author":"Lo\u0308ser","year":"2005","journal-title":"J. Med. Chem."},{"key":"2026090313174045700_cit50","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/978-1-0716-0635-3_12","article-title":"Structural and Functional Characterization\nof Schistosoma mansoni Cathepsin B1","volume":"2151","author":"Ji\u0301lkova\u0301","year":"2020","journal-title":"Methods Mol. Biol."},{"issue":"7","key":"2026090313174045700_cit51","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1140\/epjp\/i2015-15141-2","article-title":"The macromolecular crystallography\nbeamlines at BESSY II of the Helmholtz-Zentrum Berlin: Current status\nand perspectives","volume":"130","author":"Mueller","year":"2015","journal-title":"Eur. Phys. J. Plus"},{"issue":"2","key":"2026090313174045700_cit52","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1107\/S0907444909047337","article-title":"Xds","volume":"66","author":"Kabsch","year":"2010","journal-title":"Acta Crystallogr.,\nSect. D: Biol. Crystallogr."},{"issue":"12","key":"2026090313174045700_cit53","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1107\/S0907444900013780","article-title":"An approach\nto multi-copy search in molecular replacement","volume":"56","author":"Vagin","year":"2000","journal-title":"Acta Crystallogr., Sect. D: Biol. Crystallogr."},{"issue":"4","key":"2026090313174045700_cit54","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1107\/S0907444910045749","article-title":"Overview\nof the CCP4 suite and current developments","volume":"67","author":"Winn","year":"2011","journal-title":"Acta Crystallogr., Sect. D: Biol. Crystallogr."},{"issue":"12","key":"2026090313174045700_cit55","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building\ntools for molecular graphics","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Crystallogr.,\nSect. D: Biol. Crystallogr."},{"issue":"5","key":"2026090313174045700_cit56","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1039\/P29930000799","article-title":"Cosmo - a\nNew Approach to Dielectric Screening in Solvents\nwith Explicit Expressions for the Screening Energy and Its Gradient","author":"Klamt","year":"1993","journal-title":"J. Chem. Soc., Perkin Trans. 2"},{"issue":"3","key":"2026090313174045700_cit57","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/0009-2614(89)85118-8","article-title":"Electronic-Structure\nCalculations on Workstation Computers - the Program System Turbomole","volume":"162","author":"Ahlrichs","year":"1989","journal-title":"Chem. Phys. Lett."},{"issue":"13","key":"2026090313174045700_cit58","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1002\/jcc.24312","article-title":"Cuby: An integrative\nframework for computational chemistry","volume":"37","author":"R\u030ceza\u0301c\u030c","year":"2016","journal-title":"J. Comput.\nChem."},{"issue":"3","key":"2026090313174045700_cit59","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1002\/prot.10286","article-title":"Structure validation by C\u03b1 geometry: \u03c6,\n\u03c8 and C\u03b2 deviation","volume":"50","author":"Lovell","year":"2003","journal-title":"Proteins: Struct.,\nFunct., Genet."},{"key":"2026090313174045700_cit60","unstructured":"Case, D. A., Babin, V., Berryman, J. T., Betz, R. M., Cai, Q., Cerutti, D. S., Cheatham, T. E., Darden, T. A., Duke, R. E., Gohlke, H., Goetz, A. W., Gusarov, S., Homeyer, N., Janowski, P., Kaus, J., Kolossva\u0301ry, I., Kovalenko, A., Lee, T. S., LeGrand, S., Luchko, T., Luo, R., Madej, B., Merz, K. M., Paesani, F., Roe, D. R., Roitberg, A., Sagui, C., Salomon-Ferrer, R., Seabra, G., Simmerling, C. L., Smith, W., Swails, J., Walker, R. C., Wang, J., Wolf, R. M., Wu, X., and Kollman, P. A. (2014)  AMBER 14, University of California San Francisco, San Francisco (USA)."},{"issue":"8","key":"2026090313174045700_cit61","doi-asserted-by":"publisher","first-page":"3575","DOI":"10.1021\/acs.jctc.7b00365","article-title":"Accurate DFT-D3 Calculations in a\nSmall Basis Set","volume":"13","author":"Hostas\u030c","year":"2017","journal-title":"J. Chem. Theory Comput."},{"issue":"12","key":"2026090313174045700_cit62","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1007\/s00894-007-0233-4","article-title":"Optimization\nof parameters for semiempirical methods V: modification of NDDO approximations\nand application to 70 elements","volume":"13","author":"Stewart","year":"2007","journal-title":"J. Mol. Model."},{"issue":"1","key":"2026090313174045700_cit63","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1021\/ct200751e","article-title":"Advanced Corrections of Hydrogen Bonding and Dispersion for Semiempirical\nQuantum Mechanical Methods","volume":"8","author":"R\u030ceza\u0301c\u030c","year":"2012","journal-title":"J. Chem. Theory\nComput."},{"issue":"2","key":"2026090313174045700_cit64","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s00894-004-0183-z","article-title":"Optimization\nof parameters for semiempirical methods IV: extension of MNDO, AM1,\nand PM3 to more main group elements","volume":"10","author":"Stewart","year":"2004","journal-title":"J. Mol.\nModel."},{"issue":"39","key":"2026090313174045700_cit65","doi-asserted-by":"publisher","first-page":"12666","DOI":"10.1021\/jp1032965","article-title":"A reliable docking\/scoring\nscheme\nbased on the semiempirical quantum mechanical PM6-DH2 method accurately\ncovering dispersion and H-bonding: HIV-1 protease with 22 ligands","volume":"114","author":"Fanfrli\u0301k","year":"2010","journal-title":"J. Phys. Chem. B"},{"issue":"9","key":"2026090313174045700_cit66","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1002\/cplu.201300199","article-title":"The Semiempirical\nQuantum Mechanical Scoring Function for In Silico Drug Design","volume":"78","author":"Leps\u030ci\u0301k","year":"2013","journal-title":"ChemPlusChem"},{"issue":"14","key":"2026090313174045700_cit67","doi-asserted-by":"publisher","first-page":"4538","DOI":"10.1021\/jp809094y","article-title":"Performance of SM6, SM8, and SMD\non the SAMPL1 test set for the prediction of small-molecule solvation\nfree energies","volume":"113","author":"Marenich","year":"2009","journal-title":"J. Phys. Chem. B"},{"key":"2026090313174045700_cit68","unstructured":"Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Petersson, G. A., Nakatsuji, H., Li, X., Caricato, M., Marenich, A. V., Bloino, J., Janesko, B. G., Gomperts, R., Mennucci, B., Hratchian, H. P., Ortiz, J. V., Izmaylov, A. F., Sonnenberg, J. L., Williams Ding, F., Lipparini, F., Egidi, F., Goings, J., Peng, B., Petrone, A., Henderson, T., Ranasinghe, D., Zakrzewski, V. G., Gao, J., Rega, N., Zheng, G., Liang, W., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Throssell, K., Montgomery, J. A., Jr., Peralta, J. E., Ogliaro, F., Bearpark, M. J., Heyd, J. J., Brothers, E. N., Kudin, K. N., Staroverov, V. N., Keith, T. A., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A. P., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Millam, J. M., Klene, M., Adamo, C., Cammi, R., Ochterski, J. W., Martin, R. L., Morokuma, K., Farkas, O., Foresman, J. B., and Fox, D. J. (2016)  Gaussian 16, Rev. C.01, Gaussian, Inc., Wallingford (USA)."},{"issue":"6","key":"2026090313174045700_cit69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003827","article-title":"Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors","volume":"9","author":"Fajtova\u0301","year":"2015","journal-title":"PLoS Neglected Trop. Dis."},{"issue":"7","key":"2026090313174045700_cit70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000478","article-title":"Drug discovery\nfor schistosomiasis: hit and lead compounds identified in a library\nof known drugs by medium-throughput phenotypic screening","volume":"3","author":"Abdulla","year":"2009","journal-title":"PLoS Neglected Trop. Dis."},{"issue":"10","key":"2026090313174045700_cit71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000850","article-title":"RNA Interference in Schistosoma mansoni Schistosomula: Selectivity, Sensitivity and Operation\nfor Larger-Scale Screening","volume":"4","author":"S\u030ctefanic\u0301","year":"2010","journal-title":"PLoS Neglected Trop.\nDis."},{"key":"2026090313174045700_cit72","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/978-1-0716-0635-3_5","article-title":"Collection\nof Excretory\/Secretory Products from Individual Developmental Stages\nof the Blood Fluke Schistosoma mansoni","volume":"2151","author":"Leontovyc\u030c","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"2026090313174045700_cit73","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.biochi.2015.09.025","article-title":"Excretion\/secretion\nproducts from Schistosoma mansoni adults, eggs and\nschistosomula have unique peptidase specificity profiles","volume":"122","author":"Dvor\u030ca\u0301k","year":"2016","journal-title":"Biochimie"},{"issue":"6","key":"2026090313174045700_cit74","doi-asserted-by":"publisher","first-page":"10873","DOI":"10.3390\/molecules200610873","article-title":"Anti-Schistosomal\nActivity of Cinnamic Acid Esters: Eugenyl and Thymyl Cinnamate Induce\nCytoplasmic Vacuoles and Death in Schistosomula of Schistosoma mansoni","volume":"20","author":"Glaser","year":"2015","journal-title":"Molecules"},{"issue":"1","key":"2026090313174045700_cit75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004356","article-title":"Structure-Bioactivity\nRelationship for Benzimidazole Thiophene Inhibitors of Polo-Like Kinase\n1 (PLK1), a Potential Drug Target in Schistosoma mansoni","volume":"10","author":"Long","year":"2016","journal-title":"PLoS Neglected Trop. Dis."}],"container-title":["ACS Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsinfecdis.0c00644","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/7\/1\/189\/67303736\/acsinfecdis.0c00644.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/7\/1\/189\/67303736\/acsinfecdis.0c00644.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:17:52Z","timestamp":1788455872000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article\/7\/1\/189\/468055\/Azanitrile-Inhibitors-of-the-SmCB1-Protease-Target"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,10]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12,10]]},"published-print":{"date-parts":[[2021,1,8]]}},"URL":"https:\/\/doi.org\/10.1021\/acsinfecdis.0c00644","relation":{},"ISSN":["2373-8227"],"issn-type":[{"value":"2373-8227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,10]]}}}