{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:42:33Z","timestamp":1787877753433,"version":"build-2784847793"},"reference-count":45,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T00:00:00Z","timestamp":1594598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003088","name":"Evangelisches Studienwerk Villigst","doi-asserted-by":"publisher","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/501100003088","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Juergen Manchot-Stiftung","award":["None"],"award-info":[{"award-number":["None"]}]},{"name":"Open Access Publication Funds of the Technische Universit\u00e4t Braunschweig","award":["None"],"award-info":[{"award-number":["None"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Malaria causes hundreds of thousands of deaths every year, making it one of the most dangerous infectious diseases worldwide. Because the pathogens have developed resistance against most of the established anti-malarial drugs, new antiplasmodial agents are urgently needed. In analogy to similar antiplasmodial ketones, 4-arylthieno[2,3-b]pyridine-2-carboxamides were synthesized by Thorpe-Ziegler reactions. In contrast to the related ketones, these carboxamides are only weak inhibitors of the plasmodial enzyme PfGSK-3 but the compounds nevertheless show strong antiparasitic activity. The most potent representatives inhibit the pathogens with IC50 values in the two-digit nanomolar range and exhibit high selectivity indices (&gt;100).<\/jats:p>","DOI":"10.3390\/molecules25143187","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T05:10:30Z","timestamp":1595394630000},"page":"3187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["4-Arylthieno[2,3-b]pyridine-2-carboxamides Are a New Class of Antiplasmodial Agents"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7141-812X","authenticated-orcid":false,"given":"Sandra I.","family":"Schweda","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Medizinische und Pharmazeutische Chemie, Technische Universit\u00e4t Braunschweig, 38106 Braunschweig, Germany"},{"name":"Zentrum f\u00fcr Pharmaverfahrenstechnik (PVZ), Technische Universit\u00e4t Braunschweig, Franz-Liszt-Stra\u00dfe 35A, 38106 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Alder","sequence":"additional","affiliation":[{"name":"Centre for Structural Systems Biology, 22607 Hamburg, Germany"},{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"},{"name":"Department of Biology, University of Hamburg, 20146 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7965-8272","authenticated-orcid":false,"given":"Tim","family":"Gilberger","sequence":"additional","affiliation":[{"name":"Centre for Structural Systems Biology, 22607 Hamburg, Germany"},{"name":"Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany"},{"name":"Department of Biology, University of Hamburg, 20146 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-5322","authenticated-orcid":false,"given":"Conrad","family":"Kunick","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische und Pharmazeutische Chemie, Technische Universit\u00e4t Braunschweig, 38106 Braunschweig, Germany"},{"name":"Zentrum f\u00fcr Pharmaverfahrenstechnik (PVZ), Technische Universit\u00e4t Braunschweig, Franz-Liszt-Stra\u00dfe 35A, 38106 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/nature24059","article-title":"The prevalence of Plasmodium falciparum in sub-saharan Africa since 1900","volume":"550","author":"Snow","year":"2017","journal-title":"Nature"},{"key":"ref_2","unstructured":"(2020). World Malaria Report 2019, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40249-016-0151-8","article-title":"Malaria: Global progress 2000\u20132015 and future challenges","volume":"5","author":"Cibulskis","year":"2016","journal-title":"Infect. Dis. Poverty"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nature15535","article-title":"The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015","volume":"526","author":"Bhatt","year":"2015","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.pt.2017.01.004","article-title":"How to contain artemisinin and multidrug-resistant falciparum malaria","volume":"33","author":"Dondorp","year":"2017","journal-title":"Trends Parasitol."},{"key":"ref_6","unstructured":"(2006). WHO Briefing on Malaria Treatment Guidelines and Artemisinin Monotherapies, World Health Organization."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1365-3156.2005.01557.x","article-title":"In vivo sensitivity monitoring of mefloquine monotherapy and artesunate-mefloquine combinations for the treatment of uncomplicated falciparum malaria in Thailand in 2003","volume":"11","author":"Vijaykadga","year":"2006","journal-title":"Trop. Med. Int. Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1056\/NEJMc0805011","article-title":"Evidence of artemisinin-resistant malaria in western Cambodia","volume":"359","author":"Noedl","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1111\/j.1365-3156.2006.01739.x","article-title":"Efficacy of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in northwest Cambodia","volume":"11","author":"Denis","year":"2006","journal-title":"Trop. Med. Int. Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nrmicro.2017.161","article-title":"Drug resistance in Plasmodium","volume":"16","author":"Haldar","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nsanzabana, C. (2019). Resistance to artemisinin combination therapies (ACTs): Do not forget the partner drug!. Trop. Med. Infect. Dis., 4.","DOI":"10.3390\/tropicalmed4010026"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00436-018-6126-x","article-title":"Current scenario and future strategies to fight artemisinin resistance","volume":"118","author":"Pasupureddy","year":"2019","journal-title":"Parasitol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s11908-017-0583-8","article-title":"Malaria 2017: Update on the clinical literature and management","volume":"19","author":"Daily","year":"2017","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1021\/jm301575n","article-title":"3,6-Diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles are selective inhibitors of Plasmodium falciparum glycogen synthase kinase-3","volume":"56","author":"Fugel","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms1558","article-title":"Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum","volume":"2","author":"Solyakov","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bbapap.2003.11.023","article-title":"Plasmodium falciparum glycogen synthase kinase-3: Molecular model, expression, intracellular localisation and selective inhibitors","volume":"1697","author":"Droucheau","year":"2004","journal-title":"BBA-Proteins Proteom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/science.aap7847","article-title":"Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis","volume":"360","author":"Zhang","year":"2018","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12936-019-2725-y","article-title":"Structure\u2013activity relationships in a series of antiplasmodial thieno[2,3-b]pyridines","volume":"18","author":"Masch","year":"2019","journal-title":"Malar. J."},{"key":"ref_19","first-page":"771","article-title":"Cyclization of nitriles. XXV. Synthesis and reactions of chalkogen-containing 6-amino-3,5-dicyanopyridines","volume":"19","author":"Sharanin","year":"1988","journal-title":"Russ. J. Org. Chem."},{"key":"ref_20","unstructured":"Brandt, W. (2009). Neue Inhibitoren der Proteinkinasen PfGSK-3 und RET. [Dissertation Thesis, Technische Universit\u00e4t Braunschweig]."},{"key":"ref_21","unstructured":"Masch, A. (2017). Neue Thieno[2,3-b]pyridine als Hemmstoffe des Malaria-Erregers Plasmodium falciparum. [Dissertation Thesis, Technische Universit\u00e4t Braunschweig]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1134\/S1070428018110106","article-title":"Synthesis of 2-alkylsulfanyl-6-amino-4-aryl-5-cyanonicotinonitriles by recyclization of 2,6-diamino-4-aryl-3,5-dicyano-4H-thiopyrans with alkyl halides","volume":"54","author":"Dyachenko","year":"2018","journal-title":"Russ. J. Org. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1007\/s11172-005-0333-1","article-title":"Thienopyridines: Synthesis, properties and biological activity","volume":"54","author":"Litvinov","year":"2005","journal-title":"Russ. Chem. Bull."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0065-2725(06)93003-7","article-title":"The chemistry of thienopyridines","volume":"93","author":"Litvinov","year":"2007","journal-title":"Adv. Heterocycl. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7979","DOI":"10.1039\/c1ob06051a","article-title":"Benzothiazines in organic synthesis. Synthesis of fluorescent 7-amino-2,1-benzothiazines","volume":"9","author":"Yongpruksa","year":"2011","journal-title":"Org. Biomol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7918","DOI":"10.1021\/jo034593i","article-title":"A one-pot synthesis of pyrido[2,3-b][1,4]oxazin-2-ones","volume":"68","author":"Cho","year":"2003","journal-title":"J. Org. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Brunskill, J.S.A., De, A., and Ewing, D.F. (1978). Dimerisation of 3-aryl-2-cyanothioacrylamides. A [2s + 4s] cyclo-addition to give substituted 3,4-dihydro-2H-thiopyrans. J. Chem. Soc. Perk. Trans. 1, 629\u2013633.","DOI":"10.1039\/p19780000629"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1016\/S0040-4020(01)81038-3","article-title":"Studies on alkylheteroaromatic compounds. The reactivity of alkyl polyfunctionally substituted azines towards electrophilic reagents","volume":"45","author":"Elnagdi","year":"1989","journal-title":"Tetrahedron"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Armarego, W.L.F., and Chai, C.L.L. (2009). Purification of Laboratory Chemicals, Butterworth-Heinemann Elsevier Ltd.. [6th ed.].","DOI":"10.1016\/B978-1-85617-567-8.50012-3"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/10426509808032459","article-title":"Organophosphorus chemistry, 29. The action of 2,4-bis-(4-methoxy-phenyl)-1,3,2,4-dithiaphosphetane-2,4-disulfide (Lawesson\u2032s reagent) on \u03b1, \u03b2-unsaturated nitriles","volume":"133","author":"Khidre","year":"1998","journal-title":"Phosphorus Sulfur Silicon Relat. Elem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1021\/jo01054a036","article-title":"Reactions of substituted methylenemalononitriles and their derivatives 1","volume":"27","author":"McCall","year":"1962","journal-title":"J. Org. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1134\/S1070428007020212","article-title":"Cross-recyclization of 4-aryl-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 1-morpholino-1-cyclopentene: New route to 4-aryl-2-thioxo-2,5,6,7-tetrahydro-1H-[1]pyrindine-3-carbonitriles and their derivatives","volume":"43","author":"Dyachenko","year":"2007","journal-title":"Russ. J. Org. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sharanin, Y.A., Promonenkov, V.K., and Shestopalov, A.M. (1982). Recycyclization of 4-amino-6-aryl-5-cyano-1,3-dithia-4-cyclohexene-2-spirocycloalkanes to 4-aryl-3-cyano-5,6-polymethylenepyridine-2(1H)-thiones. Russ. J. Org. Chem., 1782\u20131783.","DOI":"10.1002\/chin.198249122"},{"key":"ref_34","first-page":"1539","article-title":"Cyclization of nitriles. X. Enaminonitriles of the 1,3-dithia-4-cyclohexene series and their recyclization into pyridine and thiazole derivatives","volume":"15","author":"Sharanin","year":"1984","journal-title":"Russ. J. Org. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sharanin, Y.A., and Shestopalov, A.M. (1989). Cyclization of nitriles. XXXIV. Transformation of 4-aryl-2,6-diamino-3,5-dicyano-4H-thiopyrans into substituted 4-aryl-3-cyano-2(1H)-pyridinethiones and 2-amino-4-aryl-7,7-dimethyl-5-oxo-3-cyano-5,6,7,8-tetrahydro-4H-benzo[b]pyrans. Russ. J. Org. Chem., 1331\u20131335.","DOI":"10.1002\/chin.198941188"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1134\/S1070428008030172","article-title":"Synthesis of 4-alkyl(aryl, hetaryl)-2-thioxo-5,6,7,8-tetrahydroquinoline-3-carbonitriles and their derivatives by cross-recyclization of 4-alkyl(aryl, hetaryl)-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 4-(cyclohex-1-en-1-yl)-morpholine, alkyl halides and cyclohexanone","volume":"44","author":"Dyachenko","year":"2008","journal-title":"Russ. J. Org. Chem."},{"key":"ref_37","first-page":"358","article-title":"Synthese von 4-Aryl-3-cyan-5,6,7,8-tetrahydro-chinolin-2(1H)-thionen sowie von 3-Cyan-4-phenyl-6,7,8,9-tetrahydro-5H-cyclohepta-pyrid-2(1H)-thion und davon abgeleitete Thieno-Derivate","volume":"43","author":"Vieweg","year":"1988","journal-title":"Pharmazie"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1021\/jo01048a010","article-title":"The reaction of vinyl chloroacetate with some nucleophilic reagents","volume":"27","author":"Hauser","year":"1962","journal-title":"J. Org. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1139\/v79-314","article-title":"Synthesis and reactivity of 2-sulfonyl-2-haloaziridines","volume":"57","author":"Gaillot","year":"1979","journal-title":"Can. J. Chem."},{"key":"ref_40","unstructured":"Biel, J.H., and Warawa, E.J. (1968). N-Aryl-N\u2032-Cyclopropyl-Ethylene Diamine Derivatives. (3365458), U.S. Patent."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/10426500008076538","article-title":"Synthesis of some new thieno[2,3-b]pyridines, pyrido[3\u2032,2\u2032:4,5]-thieno[3,2-d]pyrimidines and pyrido[3\u2032,2\u2032:4,5]thieno[3,2-d][1,2,3]-triazines","volume":"166","author":"Bakhite","year":"2000","journal-title":"Phosphorus Sulfur Silicon Relat. Elem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/gkm047","article-title":"A versatile ligation-independent cloning method suitable for high-throughput expression screening applications","volume":"35","author":"Berrow","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1128\/AAC.48.5.1803-1806.2004","article-title":"Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening","volume":"48","author":"Smilkstein","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/srep00118","article-title":"A rapid and robust tri-color flow cytometry assay for monitoring malaria parasite development","volume":"1","author":"Malleret","year":"2011","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1126\/science.781840","article-title":"Human malaria parasites in continuous culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/14\/3187\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:50:47Z","timestamp":1760176247000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/14\/3187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,13]]},"references-count":45,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["molecules25143187"],"URL":"https:\/\/doi.org\/10.3390\/molecules25143187","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,13]]}}}