{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:36:51Z","timestamp":1791549411903,"version":"4.3.4"},"reference-count":76,"publisher":"Bentham Science Publishers Ltd.","issue":"15","funder":[{"DOI":"10.13039\/501100003407","name":"MIUR","doi-asserted-by":"publisher","award":["FFABR 2017"],"award-info":[{"award-number":["FFABR 2017"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CMC"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n<jats:title\/>\n<jats:p>Malaria remains a serious problem in global public health, particularly widespread\nin South America and in tropical regions of Africa and Asia. Chemotherapy is actually the\nonly way to treat this poverty-related disease, since an effective vaccine is not currently\navailable. However, the onset of resistance to the most common antimalarial drugs sometimes\nmakes the current therapeutic regimen problematic. Therefore, the identification of new targets\nfor a new drug discovery process is an urgent priority. In this context, falcipain-2 and falcipain-\n3 of P. falciparum represent the key enzymes in the life-cycle of the parasite. Both falcipain-\n2 and falcipain-3 are involved in hemoglobin hydrolysis, an essential pathway to provide\nfree amino acids for the parasite metabolic needs. In addition, falcipain-2 is involved in\ncleaving ankirin and band 4.1 protein, which are cytoskeletal elements essential for the stability\nof the red cell membrane. This review article is focused on the most recent and effective\ninhibitors of falcipain-2 and falcipain-3, with particular attention to peptide, peptidomimetic\nor nonpeptide inhibitors, which targeted one or both the malarial cysteine proteases, endowed\nwith a consistent activity against P. falciparum.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/0929867327666200730215316","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T17:31:53Z","timestamp":1596475913000},"page":"3010-3031","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Falcipain-2 and Falcipain-3 Inhibitors as Promising Antimalarial Agents"],"prefix":"10.2174","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9020-2068","authenticated-orcid":true,"given":"Roberta","family":"Ettari","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8473-3321","authenticated-orcid":true,"given":"Santo","family":"Previti","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3191-3932","authenticated-orcid":true,"given":"Carla","family":"Di Chio","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-797X","authenticated-orcid":true,"given":"Maria","family":"Zappal\u00e0","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref=1","unstructured":"WHO, The \"World malaria report 2019\" at a glance. Available\nat:  [accessed on: April 15th\n2021]."},{"key":"ref=2","unstructured":"WHO, Emergency response to artemisinin resistance in the\nGreater Mekong subregion. Regional framework for action\n2013-2015 (archived). Available at:  [accessed on:\nApril 15th 2021]."},{"key":"ref=3","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/med.20163","volume":"30","author":"Ettari R.","year":"2010","unstructured":"Ettari R.; Bova F.; Zappal\u00e0 M.; Grasso S.; Micale N.; Falcipain-2 inhibitors. Med Res Rev 2010,30(1),136-167","journal-title":"Med Res Rev"},{"key":"ref=4","doi-asserted-by":"publisher","first-page":"8840","DOI":"10.1073\/pnas.0601876103","volume":"103","author":"Liu J.","year":"2006","unstructured":"Liu J.; Istvan E.S.; Gluzman I.Y.; Gross J.; Goldberg D.E.; Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems. Proc Natl Acad Sci USA 2006,103(23),8840-8845","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref=5","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/0020-711X(70)90033-9","volume":"1","author":"Sherman I.W.","year":"1970","unstructured":"Sherman I.W.; Tanigoshi L.; Incorporation of 14C-amino-acids by malaria (Plasmodium lophurae) IV.in vivo utilization of host cell haemoglobin. Int J Biochem 1970,1(5),635-637","journal-title":"Int J Biochem"},{"key":"ref=6","first-page":"265","volume":"55","author":"Sherman I.W.","year":"1977","unstructured":"Sherman I.W.; Amino acid metabolism and protein synthesis in malarial parasites. Bull World Health Organ 1977,55(2-3),265-276","journal-title":"Bull World Health Organ"},{"key":"ref=7","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1126\/science.1077426","volume":"298","author":"Greenbaum D.C.","year":"2002","unstructured":"Greenbaum D.C.; Baruch A.; Grainger M.; Bozdech Z.; Medzihradszky K.F.; Engel J.; DeRisi J.; Holder A.A.; Bogyo M.; A role for the protease falcipain 1 in host cell invasion by the human malaria parasite. Science 2002,298(5600),2002-2006","journal-title":"Science"},{"key":"ref=8","doi-asserted-by":"publisher","first-page":"29000","DOI":"10.1074\/jbc.M004459200","volume":"275","author":"Shenai B.R.","year":"2000","unstructured":"Shenai B.R.; Sijwali P.S.; Singh A.; Rosenthal P.J.; Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum. J Biol Chem 2000,275(37),29000-29010","journal-title":"J Biol Chem"},{"key":"ref=9","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1042\/BJ20060422","volume":"399","author":"Ramjee M.K.","year":"2006","unstructured":"Ramjee M.K.; Flinn N.S.; Pemberton T.P.; Quibell M.; Wang Y.; Watts J.P.; Substrate mapping and inhibitor profiling of falcipain-2, falcipain-3 and berghepain-2: implications for peptidase anti-malarial drug discovery. Biochem J 2006,399(1),47-57","journal-title":"Biochem J"},{"key":"ref=10","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1182\/blood-2002-01-0101","volume":"100","author":"Hanspal M.","year":"2002","unstructured":"Hanspal M.; Dua M.; Takakuwa Y.; Chishti A.H.; Mizuno A.; Plasmodium falciparum cysteine protease falcipain-2 cleaves erythrocyte membrane skeletal proteins at late stages of parasite development. Blood 2002,100(3),1048-1054","journal-title":"Blood"},{"key":"ref=11","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.molbiopara.2004.11.009","volume":"139","author":"Dahl E.L.","year":"2005","unstructured":"Dahl E.L.; Rosenthal P.J.; Biosynthesis, localization, and processing of falcipain cysteine proteases of Plasmodium falciparum. Mol Biochem Parasitol 2005,139(2),205-212","journal-title":"Mol Biochem Parasitol"},{"key":"ref=12","doi-asserted-by":"publisher","first-page":"11503","DOI":"10.1073\/pnas.0600489103","volume":"103","author":"Wang S.X.","year":"2006","unstructured":"Wang S.X.; Pandey K.C.; Somoza J.R.; Sijwali P.S.; Kortemme T.; Brinen L.S.; Fletterick R.J.; Rosenthal P.J.; McKerrow J.H.; Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease. Proc Natl Acad Sci USA 2006,103(31),11503-11508","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref=13","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1021\/jm8013663","volume":"52","author":"Kerr I.D.","year":"2009","unstructured":"Kerr I.D.; Lee J.H.; Pandey K.C.; Harrison A.; Sajid M.; Rosenthal P.J.; Brinen L.S.; Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity. J Med Chem 2009,52(3),852-857","journal-title":"J Med Chem"},{"key":"ref=14","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1186\/s12936-019-3043-0","volume":"18","author":"Machin J.M.","year":"2019","unstructured":"Machin J.M.; Kantsadi A.L.; Vakonakis I.; The complex of Plasmodium falciparum falcipain-2 protease with an (E)-chalcone-based inhibitor highlights a novel, small, molecule-binding site. Malar J 2019,18(1),388-388","journal-title":"Malar J"},{"key":"ref=15","doi-asserted-by":"publisher","first-page":"25425","DOI":"10.1074\/jbc.M603776200","volume":"281","author":"Hogg T.","year":"2006","unstructured":"Hogg T.; Nagarajan K.; Herzberg S.; Chen L.; Shen X.; Jiang H.; Wecke M.; Blohmke C.; Hilgenfeld R.; Schmidt C.L.; Structural and functional characterization of Falcipain-2, a hemoglobinase from the malarial parasite Plasmodium falciparum. J Biol Chem 2006,281(35),25425-25437","journal-title":"J Biol Chem"},{"key":"ref=16","doi-asserted-by":"publisher","first-page":"25697","DOI":"10.1074\/jbc.M109.014340","volume":"284","author":"Kerr I.D.","year":"2009","unstructured":"Kerr I.D.; Lee J.H.; Farady C.J.; Marion R.; Rickert M.; Sajid M.; Pandey K.C.; Caffrey C.R.; Legac J.; Hansell E.; McKerrow J.H.; Craik C.S.; Rosenthal P.J.; Brinen L.S.; Vinyl sulfones as antiparasitic agents and a structural basis for drug design. J Biol Chem 2009,284(38),25697-25703","journal-title":"J Biol Chem"},{"key":"ref=17","doi-asserted-by":"publisher","first-page":"9138","DOI":"10.1073\/pnas.0502368102","volume":"102","author":"Pandey K.C.","year":"2005","unstructured":"Pandey K.C.; Wang S.X.; Sijwali P.S.; Lau A.L.; McKerrow J.H.; Rosenthal P.J.; The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif. Proc Natl Acad Sci USA 2005,102(26),9138-9143","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref=18","doi-asserted-by":"publisher","first-page":"14910","DOI":"10.1074\/jbc.M109680200","volume":"277","author":"Sijwali P.S.","year":"2002","unstructured":"Sijwali P.S.; Shenai B.R.; Rosenthal P.J.; Folding of the Plasmodium falciparum cysteine protease falcipain-2 is mediated by a chaperone-like peptide and not the prodomain. J Biol Chem 2002,277(17),14910-14915","journal-title":"J Biol Chem"},{"key":"ref=19","doi-asserted-by":"publisher","first-page":"140362","DOI":"10.1016\/j.bbapap.2020.140362","volume":"1868","author":"Rosenthal P.J.","year":"2020","unstructured":"Rosenthal P.J.; Falcipain cysteine proteases of malaria parasites: an update. Biochim Biophys Acta Proteins Proteomics 2020,1868(3),140362","journal-title":"Biochim Biophys Acta Proteins Proteomics"},{"key":"ref=20","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1172\/JCI113766","volume":"82","author":"Rosenthal P.J.","year":"1988","unstructured":"Rosenthal P.J.; McKerrow J.H.; Aikawa M.; Nagasawa H.; Leech J.H.; A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum. J Clin Invest 1988,82(5),1560-1566","journal-title":"J Clin Invest"},{"key":"ref=21","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1172\/JCI115456","volume":"88","author":"Rosenthal P.J.","year":"1991","unstructured":"Rosenthal P.J.; Wollish W.S.; Palmer J.T.; Rasnick D.; Antimalarial effects of peptide inhibitors of a Plasmodium falciparum cysteine proteinase. J Clin Invest 1991,88(5),1467-1472","journal-title":"J Clin Invest"},{"key":"ref=22","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1172\/JCI116262","volume":"91","author":"Rosenthal P.J.","year":"1993","unstructured":"Rosenthal P.J.; Lee G.K.; Smith R.E.; Inhibition of a Plasmodium vinckei cysteine proteinase cures murine malaria. J Clin Invest 1993,91(3),1052-1056","journal-title":"J Clin Invest"},{"key":"ref=23","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1128\/AAC.40.7.1600","volume":"40","author":"Rosenthal P.J.","year":"1996","unstructured":"Rosenthal P.J.; Olson J.E.; Lee G.K.; Palmer J.T.; Klaus J.L.; Rasnick D.; Antimalarial effects of vinyl sulfone cysteine proteinase inhibitors. Antimicrob Agents Chemother 1996,40(7),1600-1603","journal-title":"Antimicrob Agents Chemother"},{"key":"ref=24","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/S0968-0896(99)00004-8","volume":"7","author":"Olson J.E.","year":"1999","unstructured":"Olson J.E.; Lee G.K.; Semenov A.; Rosenthal P.J.; Antimalarial effects in mice of orally administered peptidyl cysteine protease inhibitors. Bioorg Med Chem 1999,7(4),633-638","journal-title":"Bioorg Med Chem"},{"key":"ref=25","doi-asserted-by":"publisher","first-page":"3810","DOI":"10.1128\/AAC.47.12.3810-3814.2003","volume":"47","author":"Lee B.J.","year":"2003","unstructured":"Lee B.J.; Singh A.; Chiang P.; Kemp S.J.; Goldman E.A.; Weinhouse M.I.; Vlasuk G.P.; Rosenthal P.J.; Antimalarial activities of novel synthetic cysteine protease inhibitors. Antimicrob Agents Chemother 2003,47(12),3810-3814","journal-title":"Antimicrob Agents Chemother"},{"key":"ref=26","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1016\/j.bmc.2015.02.062","volume":"23","author":"Chakka S.K.","year":"2015","unstructured":"Chakka S.K.; Kalamuddin M.; Sundararaman S.; Wei L.; Mundra S.; Mahesh R.; Malhotra P.; Mohmmed A.; Kotra L.P.; Identification of novel class of falcipain-2 inhibitors as potential antimalarial agents. Bioorg Med Chem 2015,23(9),2221-2240","journal-title":"Bioorg Med Chem"},{"key":"ref=27","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1042\/bj20020753","volume":"368","author":"Singh A.","year":"2002","unstructured":"Singh A.; Shenai B.R.; Choe Y.; Gut J.; Sijwali P.S.; Craik C.S.; Rosenthal P.J.; Critical role of amino acid 23 in mediating activity and specificity of vinckepain-2, a papain-family cysteine protease of rodent malaria parasites. Biochem J 2002,368(Pt 1),273-281","journal-title":"Biochem J"},{"key":"ref=28","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1016\/j.bmcl.2018.03.069","volume":"28","author":"Nizi E.","year":"2018","unstructured":"Nizi E.; Sferrazza A.; Fabbrini D.; Nardi V.; Andreini M.; Graziani R.; Gennari N.; Bresciani A.; Paonessa G.; Harper S.; Peptidomimetic nitrile inhibitors of malarial protease falcipain-2 with high selectivity against human cathepsins. Bioorg Med Chem Lett 2018,28(9),1540-1544","journal-title":"Bioorg Med Chem Lett"},{"key":"ref=29","doi-asserted-by":"publisher","first-page":"6129","DOI":"10.1021\/jm100556b","volume":"53","author":"Coter\u00f3n J.M.","year":"2010","unstructured":"Coter\u00f3n J.M.; Catterick D.; Castro J.; Chaparro M.J.; D\u00edaz B.; Fern\u00e1ndez E.; Ferrer S.; Gamo F.J.; Gordo M.; Gut J.; de las Heras L.; Legac J.; Marco M.; Miguel J.; Mu\u00f1oz V.; Porras E.; de la Rosa J.C.; Ruiz J.R.; Sandoval E.; Ventosa P.; Rosenthal P.J.; Fiandor J.M.; Falcipain inhibitors: optimization studies of the 2-pyrimidinecarbonitrile lead series. J Med Chem 2010,53(16),6129-6152","journal-title":"J Med Chem"},{"key":"ref=30","doi-asserted-by":"publisher","first-page":"e1023","DOI":"10.1371\/journal.pntd.0001023","volume":"5","author":"Ang K.K.","year":"2011","unstructured":"Ang K.K.; Ratnam J.; Gut J.; Legac J.; Hansell E.; Mackey Z.B.; Skrzypczynska K.M.; Debnath A.; Engel J.C.; Rosenthal P.J.; McKerrow J.H.; Arkin M.R.; Renslo A.R.; Mining a cathepsin inhibitor library for new antiparasitic drug leads. PLoS Negl Trop Dis 2011,5(5),e1023","journal-title":"PLoS Negl Trop Dis"},{"key":"ref=31","doi-asserted-by":"publisher","first-page":"4624","DOI":"10.1016\/j.bmc.2018.07.015","volume":"26","author":"Royo S.","year":"2018","unstructured":"Royo S.; Schirmeister T.; Kaiser M.; Jung S.; Rodr\u00edguez S.; Bautista J.M.; Gonz\u00e1lez F.V.; Antiprotozoal and cysteine proteases inhibitory activity of dipeptidyl enoates. Bioorg Med Chem 2018,26(16),4624-4634","journal-title":"Bioorg Med Chem"},{"key":"ref=32","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1016\/j.bmcl.2014.01.062","volume":"24","author":"Weldon D.J.","year":"2014","unstructured":"Weldon D.J.; Shah F.; Chittiboyina A.G.; Sheri A.; Chada R.R.; Gut J.; Rosenthal P.J.; Shivakumar D.; Sherman W.; Desai P.; Jung J.C.; Avery M.A.; Synthesis, biological evaluation, hydration site thermodynamics, and chemical reactivity analysis of \u03b1-keto substituted peptidomimetics for the inhibition of Plasmodium falciparum. Bioorg Med Chem Lett 2014,24(5),1274-1279","journal-title":"Bioorg Med Chem Lett"},{"key":"ref=33","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1016\/j.chembiol.2012.09.020","volume":"19","author":"Stolze S.C.","year":"2012","unstructured":"Stolze S.C.; Deu E.; Kaschani F.; Li N.; Florea B.I.; Richau K.H.; Colby T.; van der Hoorn R.A.L.; Overkleeft H.S.; Bogyo M.; Kaiser M.; The antimalarial natural product symplostatin 4 is a nanomolar inhibitor of the food vacuole falcipains. Chem Biol 2012,19(12),1546-1555","journal-title":"Chem Biol"},{"key":"ref=34","doi-asserted-by":"publisher","first-page":"5576","DOI":"10.1021\/ol1024663","volume":"12","author":"Conroy T.","year":"2010","unstructured":"Conroy T.; Guo J.T.; Hunt N.H.; Payne R.J.; Total synthesis and antimalarial activity of symplostatin 4. Org Lett 2010,12(23),5576-5579","journal-title":"Org Lett"},{"key":"ref=35","doi-asserted-by":"publisher","first-page":"10557","DOI":"10.1021\/jm501439w","volume":"57","author":"Conroy T.","year":"2014","unstructured":"Conroy T.; Guo J.T.; Elias N.; Cergol K.M.; Gut J.; Legac J.; Khatoon L.; Liu Y.; McGowan S.; Rosenthal P.J.; Hunt N.H.; Payne R.J.; Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials. J Med Chem 2014,57(24),10557-10563","journal-title":"J Med Chem"},{"key":"ref=36","doi-asserted-by":"publisher","first-page":"5562","DOI":"10.1021\/acs.jmedchem.9b00504","volume":"62","author":"Stoye A.","year":"2019","unstructured":"Stoye A.; Juillard A.; Tang A.H.; Legac J.; Gut J.; White K.L.; Charman S.A.; Rosenthal P.J.; Grau G.E.R.; Hunt N.H.; Payne R.J.; Falcipain inhibitors based on the natural product gallinamide A are potent in vitro andin vivo antimalarials. J Med Chem 2019,62(11),5562-5578","journal-title":"J Med Chem"},{"key":"ref=37","doi-asserted-by":"publisher","first-page":"6911","DOI":"10.1021\/acs.jmedchem.7b00405","volume":"60","author":"Previti S.","year":"2017","unstructured":"Previti S.; Ettari R.; Cosconati S.; Amendola G.; Chouchene K.; Wagner A.; Hellmich U.A.; Ulrich K.; Krauth-Siegel R.L.; Wich P.R.; Schmid I.; Schirmeister T.; Gut J.; Rosenthal P.J.; Grasso S.; Zappal\u00e0 M.; Development of novel peptide-based michael acceptors targeting rhodesain and falcipain-2 for the treatment of neglected tropical diseases (NTDs). J Med Chem 2017,60(16),6911-6923","journal-title":"J Med Chem"},{"key":"ref=38","doi-asserted-by":"publisher","first-page":"7053","DOI":"10.1016\/j.bmc.2015.09.029","volume":"23","author":"Ettari R.","year":"2015","unstructured":"Ettari R.; Pinto A.; Previti S.; Tamborini L.; Angelo I.C.; La Pietra V.; Marinelli L.; Novellino E.; Schirmeister T.; Zappal\u00e0 M.; Grasso S.; De Micheli C.; Conti P.; Development of novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation. Bioorg Med Chem 2015,23(21),7053-7060","journal-title":"Bioorg Med Chem"},{"key":"ref=39","doi-asserted-by":"publisher","first-page":"963","DOI":"10.2174\/0929867024606731","volume":"9","author":"Adessi C.","year":"2002","unstructured":"Adessi C.; Soto C.; Converting a peptide into a drug: strategies to improve stability and bioavailability. Curr Med Chem 2002,9(9),963-978","journal-title":"Curr Med Chem"},{"key":"ref=40","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1002\/cbic.201500312","volume":"17","author":"Werner H.M.","year":"2016","unstructured":"Werner H.M.; Cabalteja C.C.; Horne W.S.; Peptide backbone composition and protease susceptibility: impact of modification type, position, and tandem substitution. ChemBioChem 2016,17(8),712-718","journal-title":"ChemBioChem"},{"key":"ref=41","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1016\/S0960-894X(02)00107-5","volume":"12","author":"Lauffer D.J.","year":"2002","unstructured":"Lauffer D.J.; Mullican M.D.; A practical synthesis of (S) 3-tert-butoxycarbonylamino-2-oxo-2,3,4,5-tetrahydro-1,5-benzodiazepine-1-acetic acid methyl ester as a conformationally restricted dipeptido-mimetic for caspase-1 (ICE) inhibitors. Bioorg Med Chem Lett 2002,12(8),1225-1227","journal-title":"Bioorg Med Chem Lett"},{"key":"ref=42","doi-asserted-by":"publisher","first-page":"3064","DOI":"10.1021\/jm060405f","volume":"49","author":"Micale N.","year":"2006","unstructured":"Micale N.; Kozikowski A.P.; Ettari R.; Grasso S.; Zappal\u00e0 M.; Jeong J.J.; Kumar A.; Hanspal M.; Chishti A.H.; Novel peptidomimetic cysteine protease inhibitors as potential antimalarial agents. J Med Chem 2006,49(11),3064-3067","journal-title":"J Med Chem"},{"key":"ref=43","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1021\/jm701141u","volume":"51","author":"Ettari R.","year":"2008","unstructured":"Ettari R.; Nizi E.; Di Francesco M.E.; Dude M.A.; Pradel G.; Vic\u00edk R.; Schirmeister T.; Micale N.; Grasso S.; Zappal\u00e0 M.; Development of peptidomimetics with a vinyl sulfone warhead as irreversible falcipain-2 inhibitors. J Med Chem 2008,51(4),988-996","journal-title":"J Med Chem"},{"key":"ref=44","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1002\/cmdc.200800050","volume":"3","author":"Ettari R.","year":"2008","unstructured":"Ettari R.; Nizi E.; Di Francesco M.E.; Micale N.; Grasso S.; Zappal\u00e0 M.; Vic\u00edk R.; Schirmeister T.; Nonpeptidic vinyl and allyl phosphonates as falcipain-2 inhibitors. ChemMedChem 2008,3(7),1030-1033","journal-title":"ChemMedChem"},{"key":"ref=45","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1021\/jm900047j","volume":"52","author":"Ettari R.","year":"2009","unstructured":"Ettari R.; Micale N.; Schirmeister T.; Gelhaus C.; Leippe M.; Nizi E.; Di Francesco M.E.; Grasso S.; Zappal\u00e0 M.; Novel peptidomimetics containing a vinyl ester moiety as highly potent and selective falcipain-2 inhibitors. J Med Chem 2009,52(7),2157-2160","journal-title":"J Med Chem"},{"key":"ref=46","doi-asserted-by":"publisher","first-page":"3228","DOI":"10.1016\/j.ejmech.2010.04.003","volume":"45","author":"Ettari R.","year":"2010","unstructured":"Ettari R.; Zappal\u00e0 M.; Micale N.; Schirmeister T.; Gelhaus C.; Leippe M.; Evers A.; Grasso S.; Synthesis of novel peptidomimetics as inhibitors of protozoan cysteine proteases falcipain-2 and rhodesain. Eur J Med Chem 2010,45(7),3228-3233","journal-title":"Eur J Med Chem"},{"key":"ref=47","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1016\/j.ejmech.2011.02.058","volume":"46","author":"Ettari R.","year":"2011","unstructured":"Ettari R.; Zappal\u00e0 M.; Micale N.; Grazioso G.; Giofr\u00e8 S.; Schirmeister T.; Grasso S.; Peptidomimetics containing a vinyl ketone warhead as falcipain-2 inhibitors. Eur J Med Chem 2011,46(6),2058-2065","journal-title":"Eur J Med Chem"},{"key":"ref=48","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1002\/cmdc.201200274","volume":"7","author":"Ettari R.","year":"2012","unstructured":"Ettari R.; Micale N.; Grazioso G.; Bova F.; Schirmeister T.; Grasso S.; Zappal\u00e0 M.; Synthesis and molecular modeling studies of derivatives of a highly potent peptidomimetic vinyl ester as falcipain-2 inhibitors. ChemMedChem 2012,7(9),1594-1600","journal-title":"ChemMedChem"},{"key":"ref=49","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1128\/AAC.47.1.154-160.2003","volume":"47","author":"Shenai B.R.","year":"2003","unstructured":"Shenai B.R.; Lee B.J.; Alvarez-Hernandez A.; Chong P.Y.; Emal C.D.; Neitz R.J.; Roush W.R.; Rosenthal P.J.; Structure-activity relationships for inhibition of cysteine protease activity and development of Plasmodium falciparum by peptidyl vinyl sulfones. Antimicrob Agents Chemother 2003,47(1),154-160","journal-title":"Antimicrob Agents Chemother"},{"key":"ref=50","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1002\/cmdc.201300390","volume":"8","author":"Ettari R.","year":"2013","unstructured":"Ettari R.; Tamborini L.; Angelo I.C.; Grasso S.; Schirmeister T.; Lo Presti L.; De Micheli C.; Pinto A.; Conti P.; Development of rhodesain inhibitors with a 3-bromoisoxazoline warhead. ChemMedChem 2013,8(12),2070-2076","journal-title":"ChemMedChem"},{"key":"ref=51","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.3109\/14756366.2015.1108972","volume":"31","author":"Ettari R.","year":"2016","unstructured":"Ettari R.; Previti S.; Cosconati S.; Kesselring J.; Schirmeister T.; Grasso S.; Zappal\u00e0 M.; Synthesis and biological evaluation of novel peptidomimetics as rhodesain inhibitors. J Enzyme Inhib Med Chem 2016,31(6),1184-1191","journal-title":"J Enzyme Inhib Med Chem"},{"key":"ref=52","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1002\/cmdc.201402079","volume":"9","author":"Ettari R.","year":"2014","unstructured":"Ettari R.; Pinto A.; Tamborini L.; Angelo I.C.; Grasso S.; Zappal\u00e0 M.; Capodicasa N.; Yzeiraj L.; Gruber E.; Aminake M.N.; Pradel G.; Schirmeister T.; De Micheli C.; Conti P.; Synthesis and biological evaluation of papain-family cathepsin L-like cysteine protease inhibitors containing a 1,4-benzodiazepine scaffold as antiprotozoal agents. ChemMedChem 2014,9(8),1817-1825","journal-title":"ChemMedChem"},{"key":"ref=53","doi-asserted-by":"publisher","first-page":"3636","DOI":"10.1016\/j.bmc.2016.06.003","volume":"24","author":"Schmidt I.","year":"2016","unstructured":"Schmidt I.; Pradel G.; Sologub L.; Golzmann A.; Ngwa C.J.; Kucharski A.; Schirmeister T.; Holzgrabe U.; Bistacrine derivatives as new potent antimalarials. Bioorg Med Chem 2016,24(16),3636-3642","journal-title":"Bioorg Med Chem"},{"key":"ref=54","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1001\/jama.1994.03510370037029","volume":"271","author":"Knapp M.J.","year":"1994","unstructured":"Knapp M.J.; Knopman D.S.; Solomon P.R.; Pendlebury W.W.; Davis C.S.; Gracon S.I.; A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer\u2019s disease. JAMA The Tacrine Study Group1994,271(13),985-991","journal-title":"JAMA"},{"key":"ref=55","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1007\/BF00932261","volume":"79","author":"Bell A.","year":"1993","unstructured":"Bell A.; Wernli B.; Franklin R.M.; Effects of microtubule inhibitors on protein synthesis in Plasmodium falciparum. Parasitol Res 1993,79(2),146-152","journal-title":"Parasitol Res"},{"key":"ref=56","doi-asserted-by":"publisher","first-page":"1700251","DOI":"10.1002\/ardp.201700251","volume":"351","author":"Sharma K.","year":"2018","unstructured":"Sharma K.; Shrivastava A.; Mehra R.N.; Deora G.S.; Alam M.M.; Zaman M.S.; Akhter M.; Synthesis of novel benzimidazole acrylonitriles for inhibition of Plasmodium falciparum growth by dual target inhibition. Arch Pharm (Weinheim) 2018,351(1),1700251","journal-title":"Arch Pharm (Weinheim)"},{"key":"ref=57","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1016\/j.bmc.2015.02.029","volume":"23","author":"Singh A.K.","year":"2015","unstructured":"Singh A.K.; Rajendran V.; Pant A.; Ghosh P.C.; Singh N.; Latha N.; Garg S.; Pandey K.C.; Singh B.K.; Rathi B.; Design, synthesis and biological evaluation of functionalized phthalimides: a new class of antimalarials and inhibitors of falcipain-2, a major hemoglobinase of malaria parasite. Bioorg Med Chem 2015,23(8),1817-1827","journal-title":"Bioorg Med Chem"},{"key":"ref=58","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1128\/AAC.38.7.1470","volume":"38","author":"Chen M.","year":"1994","unstructured":"Chen M.; Theander T.G.; Christensen S.B.; Hviid L.; Zhai L.; Kharazmi A.; Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from P. yoelii infection. Antimicrob Agents Chemother 1994,38(7),1470-1475","journal-title":"Antimicrob Agents Chemother"},{"key":"ref=59","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1002\/cmdc.201300399","volume":"9","author":"Belluti F.","year":"2014","unstructured":"Belluti F.; Uliassi E.; Veronesi G.; Bergamini C.; Kaiser M.; Brun R.; Viola A.; Fato R.; Michels P.A.; Krauth-Siegel R.L.; Cavalli A.; Bolognesi M.L.; Toward the development of dual-targeted glyceraldehyde-3-phosphate dehydrogenase\/trypanothione reductase inhibitors against Trypanosoma brucei and Trypanosoma cruzi. ChemMedChem 2014,9(2),371-382","journal-title":"ChemMedChem"},{"key":"ref=60","doi-asserted-by":"publisher","first-page":"7318","DOI":"10.1021\/bi400852h","volume":"52","author":"Lamb K.M.","year":"2013","unstructured":"Lamb K.M.; G-Dayanandan, N.; Wright, D.L.; Anderson, A.C. Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase. Biochemistry 2013,52(41),7318-7326","journal-title":"Biochemistry"},{"key":"ref=61","doi-asserted-by":"publisher","first-page":"11221","DOI":"10.1021\/cr500543f","volume":"114","author":"Barnett D.S.","year":"2014","unstructured":"Barnett D.S.; Guy R.K.; Antimalarials in development in 2014. Chem Rev 2014,114(22),11221-11241","journal-title":"Chem Rev"},{"key":"ref=62","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1016\/j.bmcl.2011.12.011","volume":"22","author":"Huang H.","year":"2012","unstructured":"Huang H.; Lu W.; Li X.; Cong X.; Ma H.; Liu X.; Zhang Y.; Che P.; Ma R.; Li H.; Shen X.; Jiang H.; Huang J.; Zhu J.; Design and synthesis of small molecular dual inhibitor of falcipain-2 and dihydrofolate reductase as antimalarial agent. Bioorg Med Chem Lett 2012,22(2),958-962","journal-title":"Bioorg Med Chem Lett"},{"key":"ref=63","doi-asserted-by":"publisher","first-page":"6467","DOI":"10.1016\/j.bmc.2017.10.017","volume":"25","author":"Chen W.","year":"2017","unstructured":"Chen W.; Huang Z.; Wang W.; Mao F.; Guan L.; Tang Y.; Jiang H.; Li J.; Huang J.; Jiang L.; Zhu J.; Discovery of new antimalarial agents: Second-generation dual inhibitors against FP-2 and PfDHFR via fragments assembely. Bioorg Med Chem 2017,25(24),6467-6478","journal-title":"Bioorg Med Chem"},{"key":"ref=64","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1128\/AAC.01526-09","volume":"54","author":"Nzila A.","year":"2010","unstructured":"Nzila A.; Rottmann M.; Chitnumsub P.; Kiara S.M.; Kamchonwongpaisan S.; Maneeruttanarungroj C.; Taweechai S.; Yeung B.K.; Goh A.; Lakshminarayana S.B.; Zou B.; Wong J.; Ma N.L.; Weaver M.; Keller T.H.; Dartois V.; Wittlin S.; Brun R.; Yuthavong Y.; Diagana T.T.; Preclinical evaluation of the antifolate QN254, 5-chloro- N\u20196\u2032-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate. Antimicrob Agents Chemother 2010,54(6),2603-2610","journal-title":"Antimicrob Agents Chemother"},{"key":"ref=65","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.bioorg.2017.01.010","volume":"71","author":"Dheer D.","year":"2017","unstructured":"Dheer D.; Singh V.; Shankar R.; Medicinal attributes of 1,2,3-triazoles: current developments. Bioorg Chem 2017,71,30-54","journal-title":"Bioorg Chem"},{"key":"ref=66","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.ejmech.2019.01.047","volume":"166","author":"Chu X.M.","year":"2019","unstructured":"Chu X.M.; Wang C.; Wang W.L.; Liang L.L.; Liu W.; Gong K.K.; Sun K.L.; Triazole derivatives and their antiplasmodial and antimalarial activities. Eur J Med Chem 2019,166,206-223","journal-title":"Eur J Med Chem"},{"key":"ref=67","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1039\/c1md00129a","volume":"2","author":"Shah F.","year":"2011","unstructured":"Shah F.; Wu Y.; Gut J.; Pedduri Y.; Legac J.; Rosenthal P.J.; Avery M.A.; Design, synthesis and biological evaluation of novel benzothiazole and triazole analogs as falcipain inhibitors. MedChemComm 2011,2(12),1201-1207","journal-title":"MedChemComm"},{"key":"ref=68","doi-asserted-by":"publisher","first-page":"39410","DOI":"10.1039\/C9RA06571G","volume":"9","author":"Singh A.","year":"2019","unstructured":"Singh A.; Kalamuddin M.; Mohmmed A.; Malhotra P.; Hoda N.; Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage. RSC Advances 2019,9(67),39410-39421","journal-title":"RSC Advances"},{"key":"ref=69","doi-asserted-by":"publisher","first-page":"115155","DOI":"10.1016\/j.bmc.2019.115155","volume":"28","author":"Rana D.","year":"2020","unstructured":"Rana D.; Kalamuddin M.; Sundriyal S.; Jaiswal V.; Sharma G.; Das Sarma K.; Sijwali P.S.; Mohmmed A.; Malhotra P.; Mahindroo N.; Identification of antimalarial leads with dual falcipain-2 and falcipain-3 inhibitory activity. Bioorg Med Chem 2020,28(1),115155","journal-title":"Bioorg Med Chem"},{"key":"ref=70","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1021\/ci200029y","volume":"51","author":"Shah F.","year":"2011","unstructured":"Shah F.; Mukherjee P.; Gut J.; Legac J.; Rosenthal P.J.; Tekwani B.L.; Avery M.A.; Identification of novel malarial cysteine protease inhibitors using structure-based virtual screening of a focused cysteine protease inhibitor library. J Chem Inf Model 2011,51(4),852-864","journal-title":"J Chem Inf Model"},{"key":"ref=71","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-374194-3.00015-9","author":"Ciapetti P.","year":"2008","unstructured":"Ciapetti P.; Giethlen B.;  The Practice of Medicinal Chemistry 2008","journal-title":"The Practice of Medicinal Chemistry"},{"key":"ref=72","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1039\/C1MD00129A","volume":"2","author":"Shah F.","year":"2011","unstructured":"Shah F.; Wu Y.; Gut J.; Pedduri Y.; Legac J.; Rosenthal P.J.; Avery M.A.; Design, synthesis and biological avaluation of novel benzothiazole and triazole analogs as falcipain inhibitors. Med Chem 2011,2,1201-1207","journal-title":"Med Chem"},{"key":"ref=73","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1046\/j.1365-2672.2000.01168.x","volume":"89","author":"Hasne M.","year":"2000","unstructured":"Hasne M.; Barrett M.P.; Drug uptake via nutrient transporters in Trypanosoma brucei. J Appl Microbiol 2000,89(4),697-701","journal-title":"J Appl Microbiol"},{"key":"ref=74","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/978-0-387-77570-8_3","volume":"625","author":"Landfear S.M.","year":"2008","unstructured":"Landfear S.M.; Drugs and transporters in kinetoplastid protozoa. Adv Exp Med Biol 2008,625,22-32","journal-title":"Adv Exp Med Biol"},{"key":"ref=75","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.addr.2009.11.024","volume":"62","author":"Santos-Magalh\u00e3es N.S.","year":"2010","unstructured":"Santos-Magalh\u00e3es N.S.; Mosqueira V.C.; Nanotechnology applied to the treatment of malaria. Adv Drug Deliv Rev 2010,62(4-5),560-575","journal-title":"Adv Drug Deliv Rev"},{"key":"ref=76","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1016\/j.addr.2006.09.009","volume":"58","author":"Torchilin V.P.","year":"2006","unstructured":"Torchilin V.P.; Multifunctional nanocarriers. Adv Drug Deliv Rev 2006,58(14),1532-1555","journal-title":"Adv Drug Deliv Rev"}],"container-title":["Current Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0929867327666200730215316","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/184419\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0929867327666200730215316","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T07:51:47Z","timestamp":1655797907000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/184419\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":76,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/0929867327666200730215316","relation":{},"ISSN":["0929-8673"],"issn-type":[{"value":"0929-8673","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2020-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-01","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}