{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:47:08Z","timestamp":1787316428965,"version":"build-2736575974"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2022,1]]},"DOI":"10.1016\/j.ejmech.2021.113913","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T15:54:04Z","timestamp":1633967644000},"page":"113913","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Synthesis and in\u00a0vitro antitrypanosomal evaluation of novel 6-heteroarylidene-substituted quinolone derivatives"],"prefix":"10.1016","volume":"227","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2813-1910","authenticated-orcid":false,"given":"Klaudia T.","family":"Angula","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2440-4993","authenticated-orcid":false,"given":"Lesetja J.","family":"Legoabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarryn","family":"Swart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich C.","family":"Hoppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6282-043X","authenticated-orcid":false,"given":"Richard M.","family":"Beteck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2021.113913_bib1","first-page":"1","article-title":"The current drug discovery landscape for trypanosomiasis and leishmaniasis: Challenges and strategies to identify drug targets","author":"Altamura","year":"2020","journal-title":"Drug Dev. Res."},{"issue":"9709","key":"10.1016\/j.ejmech.2021.113913_bib2","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0140-6736(09)60829-1","article-title":"Human african trypanosomiasis","volume":"375","author":"Brun","year":"2010","journal-title":"Lancet"},{"issue":"2","key":"10.1016\/j.ejmech.2021.113913_bib3","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/S1474-4422(12)70296-X","article-title":"Clinical features, diagnosis, and treatment of human african trypanosomiasis (sleeping sickness)","volume":"12","author":"Kennedy","year":"2013","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.ejmech.2021.113913_bib4","series-title":"Human African (Sleeping Sickness), Fact sheets","author":"Trypanosomiasis","year":"2021"},{"issue":"9","key":"10.1016\/j.ejmech.2021.113913_bib5","first-page":"2334","article-title":"Update on human african trypanosomiasis (sleeping sickness)","volume":"266","author":"Kennedy","year":"2019","journal-title":"J.\u00a0Neurol."},{"issue":"8","key":"10.1016\/j.ejmech.2021.113913_bib6","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.1128\/AAC.01757-15","article-title":"Quinolone amides as antitrypanosomal lead compounds with in\u00a0vivo activity","volume":"60","author":"Hiltensperger","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"issue":"1","key":"10.1016\/j.ejmech.2021.113913_bib7","first-page":"1","article-title":"The drugs of sleeping sickness: their mechanisms of action and resistance, and a brief history","volume":"5","author":"De Koning","year":"2020","journal-title":"Trav. Med. Infect. Dis."},{"issue":"3","key":"10.1016\/j.ejmech.2021.113913_bib8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.4066\/2591-8036.18-303","article-title":"Mechanisms of immune evasion by Trypanosoma brucei","volume":"2","author":"M\u00e1rquez-Contreras","year":"2018","journal-title":"Microbiol. Curr. Res."},{"key":"10.1016\/j.ejmech.2021.113913_bib9","first-page":"257","article-title":"Epidemiology of human african trypanosomiasis","volume":"6","author":"Franco","year":"2014","journal-title":"Clin. Epidemiol."},{"issue":"11","key":"10.1016\/j.ejmech.2021.113913_bib10","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1586\/14787210.2014.959496","article-title":"Treatment options for second-stage gambiense human african trypanosomiasis","volume":"12","author":"Eperon","year":"2014","journal-title":"Expert Rev. Anti-infect. Ther."},{"issue":"10","key":"10.1016\/j.ejmech.2021.113913_bib11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001857","article-title":"Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response","volume":"6","author":"MacLean","year":"2012","journal-title":"PLoS Neglected Trop. Dis."},{"issue":"5","key":"10.1016\/j.ejmech.2021.113913_bib12","first-page":"381","article-title":"Molecular mechanisms and therapeutic approaches to the treatment of african trypanosomiasis","volume":"4","author":"Natuva","year":"2012","journal-title":"Drug Invent. Today"},{"issue":"2","key":"10.1016\/j.ejmech.2021.113913_bib13","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/ana.21429","article-title":"The continuing problem of human african trypanosomiasis (sleeping sickness)","volume":"64","author":"Kennedy","year":"2008","journal-title":"Ann. Neurol."},{"issue":"5","key":"10.1016\/j.ejmech.2021.113913_bib14","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1179\/2047773213Y.0000000105","article-title":"A\u00a0current analysis of chemotherapy strategies for the treatment of human african trypanosomiasis","volume":"107","author":"Babokhov","year":"2013","journal-title":"Pathog. Glob. Health"},{"issue":"2","key":"10.1016\/j.ejmech.2021.113913_bib15","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0031-6997(25)00445-4","article-title":"Recent research on the biological activity of suramin","volume":"45","author":"Voogd","year":"1993","journal-title":"Pharmacol. Rev."},{"issue":"1","key":"10.1016\/j.ejmech.2021.113913_bib16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1756-3305-3-15","article-title":"The development of drugs for treatment of sleeping sickness: a historical review","volume":"3","author":"Steverding","year":"2010","journal-title":"Parasites Vectors"},{"issue":"10110","key":"10.1016\/j.ejmech.2021.113913_bib17","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/S0140-6736(17)31510-6","article-title":"Human african trypanosomiasis","volume":"390","author":"B\u00fcscher","year":"2017","journal-title":"Lancet"},{"issue":"9683","key":"10.1016\/j.ejmech.2021.113913_bib18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0140-6736(09)61117-X","article-title":"Nifurtimox-eflornithine combination therapy for second-stage african trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial","volume":"374","author":"Priotto","year":"2009","journal-title":"Lancet"},{"issue":"5","key":"10.1016\/j.ejmech.2021.113913_bib19","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/BF00926669","article-title":"The use of the 2 substituted 5-nitroimidazole, fexinidazole (hoe 239) in the treatment of chronic T.\u00a0Brucei infections in mice","volume":"69","author":"Jennings","year":"1983","journal-title":"Z\u00a0Parasitenk"},{"issue":"6","key":"10.1016\/j.ejmech.2021.113913_bib20","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0007381","article-title":"The european medicines agency's scientific opinion on oral fexinidazole for human african trypanosomiasis","volume":"13","author":"Pelfrene","year":"2019","journal-title":"PLoS Neglected Trop. Dis."},{"issue":"38","key":"10.1016\/j.ejmech.2021.113913_bib21","doi-asserted-by":"crossref","first-page":"9616","DOI":"10.1073\/pnas.1807915115","article-title":"Clinical and veterinary trypanocidal benzoxaboroles target CPSF3","volume":"115","author":"Wall","year":"2018","journal-title":"Proc. Natl. Acad. Sci. Unit. States Am."},{"issue":"10","key":"10.1016\/j.ejmech.2021.113913_bib22","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.pt.2018.08.006","article-title":"The long wait for a new drug for human african trypanosomiasis","volume":"34","author":"Baker","year":"2018","journal-title":"Trends Parasitol."},{"issue":"4","key":"10.1016\/j.ejmech.2021.113913_bib23","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1021\/ml100013s","article-title":"Discovery of novel benzoxaborole-based potent antitrypanosomal agents","volume":"1","author":"Ding","year":"2010","journal-title":"ACS Med. Chem. Lett."},{"issue":"6","key":"10.1016\/j.ejmech.2021.113913_bib24","doi-asserted-by":"crossref","first-page":"e1151","DOI":"10.1371\/journal.pntd.0001151","article-title":"Scyx-7158, an orally-active benzoxaborole for the treatment of stage 2 human african trypanosomiasis","volume":"5","author":"Jacobs","year":"2011","journal-title":"PLoS Neglected Trop. Dis."},{"issue":"12","key":"10.1016\/j.ejmech.2021.113913_bib25","doi-asserted-by":"crossref","first-page":"e923","DOI":"10.1371\/journal.pntd.0000923","article-title":"Fexinidazole\u2013a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness","volume":"4","author":"Torreele","year":"2010","journal-title":"PLoS Neglected Trop. Dis."},{"issue":"14","key":"10.1016\/j.ejmech.2021.113913_bib26","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1017\/S0031182016001268","article-title":"The animal trypanosomiases and their chemotherapy: a review","volume":"143","author":"Giordani","year":"2016","journal-title":"J.\u00a0Parasitol."},{"issue":"1","key":"10.1016\/j.ejmech.2021.113913_bib27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1756-3305-5-71","article-title":"The origins of the trypanosome genome strains Trypanosoma brucei brucei treu 927, T.\u00a0b. Gambiense dal 972, T.\u00a0Vivax y486 and T.\u00a0Congolense il3000","volume":"5","author":"Gibson","year":"2012","journal-title":"Parasites Vectors"},{"issue":"1","key":"10.1016\/j.ejmech.2021.113913_bib28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1475-2875-13-339","article-title":"Recent progress in the development of anti-malarial quinolones","volume":"13","author":"Beteck","year":"2014","journal-title":"Malar. J."},{"issue":"8","key":"10.1016\/j.ejmech.2021.113913_bib29","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1128\/AAC.43.8.2066","article-title":"Antitrypanosomal activity of fluoroquinolones","volume":"43","author":"Nenortas","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"issue":"9","key":"10.1016\/j.ejmech.2021.113913_bib30","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1128\/AAC.47.9.3015-3017.2003","article-title":"Antitrypanosomal activities of fluoroquinolones with pyrrolidinyl substitutions","volume":"47","author":"Nenortas","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ejmech.2021.113913_bib31","doi-asserted-by":"crossref","first-page":"188","DOI":"10.17159\/0379-4350\/2018\/v71a25","article-title":"Synthesis, in\u00a0vitro cytotoxicity and trypanocidal evaluation of novel 1,3,6-substituted non-fluoroquinolones","volume":"71","author":"Beteck","year":"2018","journal-title":"S.\u00a0Afr. J. Chem."},{"issue":"12","key":"10.1016\/j.ejmech.2021.113913_bib32","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1039\/C8MD00319J","article-title":"Screening of the pathogen box reveals new starting points for anti-trypanosomal drug discovery","volume":"9","author":"Veale","year":"2018","journal-title":"Medchemcomm"},{"issue":"5","key":"10.1016\/j.ejmech.2021.113913_bib33","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3390\/medicina55050206","article-title":"Anti-trypanosomal and antimalarial properties of tetralone derivatives and structurally related benzocycloalkanones","volume":"55","author":"Beteck","year":"2019","journal-title":"Medicina (Kaunas)"},{"key":"10.1016\/j.ejmech.2021.113913_bib34","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1055\/a-0775-0737","article-title":"In\u00a0vitro anti-trypanosomal activities of indanone-based chalcones","volume":"69","author":"Beteck","year":"2019","journal-title":"Drug Res."},{"issue":"1\u20132","key":"10.1016\/j.ejmech.2021.113913_bib35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J.\u00a0Immunol. Methods"},{"issue":"1","key":"10.1016\/j.ejmech.2021.113913_bib36","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3349\/ymj.1997.38.1.52","article-title":"Triton x-100 induces apoptosis in human hepatoma cell lines","volume":"38","author":"Ahn","year":"1997","journal-title":"Yonsei Med. J."},{"issue":"2","key":"10.1016\/j.ejmech.2021.113913_bib37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3390\/jfb5020043","article-title":"Hacat keratinocytes response on antimicrobial atelocollagen substrates: extent of cytotoxicity, cell viability and proliferation","volume":"5","author":"L\u00f3pez-Garc\u00eda","year":"2014","journal-title":"J.\u00a0Funct. Biomater."},{"issue":"21","key":"10.1016\/j.ejmech.2021.113913_bib38","doi-asserted-by":"crossref","first-page":"9824","DOI":"10.1021\/acs.jmedchem.9b01220","article-title":"The blood\u2013brain barrier (BBB) score","volume":"62","author":"Gupta","year":"2019","journal-title":"J.\u00a0Med. Chem."},{"issue":"4","key":"10.1016\/j.ejmech.2021.113913_bib39","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1602\/neurorx.2.4.541","article-title":"Medicinal chemical properties of successful central nervous system drugs","volume":"2","author":"Pajouhesh","year":"2005","journal-title":"NeuroRx"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523421007625?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523421007625?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:31:30Z","timestamp":1759329090000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523421007625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":39,"alternative-id":["S0223523421007625"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2021.113913","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synthesis and in\u00a0vitro antitrypanosomal evaluation of novel 6-heteroarylidene-substituted quinolone derivatives","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2021.113913","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"113913"}}