{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:06:16Z","timestamp":1788307576899,"version":"build-2803163510"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,10,7]],"date-time":"2017-10-07T00:00:00Z","timestamp":1507334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/L017180\/1"],"award-info":[{"award-number":["BB\/L017180\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Novartis Institute for Tropical Diseases"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2017,12]]},"DOI":"10.1016\/j.ejmech.2017.09.067","type":"journal-article","created":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T03:47:26Z","timestamp":1507780046000},"page":"676-689","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["African trypanosomiasis: Synthesis &amp; SAR enabling novel drug discovery of ubiquinol mimics for trypanosome alternative oxidase"],"prefix":"10.1016","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8068-9180","authenticated-orcid":false,"given":"Ryan A.","family":"West","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oran G.","family":"O'Doherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Askwith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Atack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Beswick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Laverick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Paradowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0964-2101","authenticated-orcid":false,"given":"Lewis E.","family":"Pennicott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7156-5725","authenticated-orcid":false,"given":"Srinivasa P.S.","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon E.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2017.09.067_bib1","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"},{"key":"10.1016\/j.ejmech.2017.09.067_bib2","author":"WHO Trypanosomiasis"},{"key":"10.1016\/j.ejmech.2017.09.067_bib3","doi-asserted-by":"crossref","first-page":"E2130","DOI":"10.1073\/pnas.1400699111","article-title":"Evolution of the primate trypanolytic factor APOL1","volume":"111","author":"Thomson","year":"2014","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.ejmech.2017.09.067_bib4","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1111\/j.1462-5822.2009.01383.x","article-title":"Antigenic variation in the African trypanosome: molecular mechanisms and phenotypic complexity","volume":"11","author":"Morrison","year":"2009","journal-title":"Cell. Microbiol."},{"key":"10.1016\/j.ejmech.2017.09.067_bib5","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.pt.2012.12.005","article-title":"Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story","volume":"29","author":"Baker","year":"2013","journal-title":"Trends Parasitol."},{"key":"10.1016\/j.ejmech.2017.09.067_bib6","series-title":"Cases of Sleeping Sickness Drop to Lowest Level in 75 Years","author":"WHO","year":"2015"},{"key":"10.1016\/j.ejmech.2017.09.067_bib7","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.2017.09.067_bib8","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.actatropica.2005.08.001","article-title":"Clinical aspects of 2541 patients with second stage human African trypanosomiasis","volume":"97","author":"Blum","year":"2006","journal-title":"Acta Trop."},{"key":"10.1016\/j.ejmech.2017.09.067_bib9","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.2174\/156802611795429167","article-title":"State of the art in African trypanosome drug discovery","volume":"11","author":"Jacobs","year":"2011","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.ejmech.2017.09.067_bib10","doi-asserted-by":"crossref","first-page":"e333","DOI":"10.1371\/journal.pntd.0000333","article-title":"The burden of human African trypanosomiasis","volume":"2","author":"Fevre","year":"2008","journal-title":"PLoS Negl. Trop. Dis."},{"key":"10.1016\/j.ejmech.2017.09.067_bib11","series-title":"African Trypanosomiasis-Disease Database","year":"2016"},{"issue":"5-6","key":"10.1016\/j.ejmech.2017.09.067_bib12","first-page":"595","article-title":"The effects of trypanosomiasis on rural economy","volume":"28","author":"Wilson","year":"1963","journal-title":"Bull. World Health Organ"},{"key":"10.1016\/j.ejmech.2017.09.067_bib13","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1186\/s13071-014-0603-6","article-title":"The burden and spatial distribution of bovine African trypanosomes in small holder crop-livestock production systems in Tororo District, south-eastern Uganda","volume":"7","author":"Muhanguzi","year":"2014","journal-title":"Parasit. Vectors"},{"key":"10.1016\/j.ejmech.2017.09.067_bib14","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1939-165X.2011.00295.x","article-title":"What is your diagnosis? Lymphadenopathy in a cow with severe anemia. Bovine trypanosomiasis","volume":"40","author":"Salgado","year":"2011","journal-title":"Vet. Clin. Pathol."},{"key":"10.1016\/j.ejmech.2017.09.067_bib15","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S1473-3099(13)70191-9","article-title":"Do we need new drugs against human African trypanosomiasis?","volume":"13","author":"Stich","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"10.1016\/j.ejmech.2017.09.067_bib16","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/0035-9203(95)90673-8","article-title":"Risk factors for encephalopathy Trypanosoma brucei gambiense and mortality during sleeping sickness melarsoprol treatment of","volume":"89","author":"The","year":"1995","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"10.1016\/j.ejmech.2017.09.067_bib17","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1046\/j.1365-3156.2001.00710.x","article-title":"Clinical description of encephalopathic syndromes and risk factors for their occurrence and outcome during melarsoprol treatment of human African trypanosomiasis","volume":"6","author":"Blum","year":"2001","journal-title":"Trop. Med. Int. Heal"},{"key":"10.1016\/j.ejmech.2017.09.067_bib18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/167147a0","article-title":"Acquired resistance to \u201cMelarsen\u201d, Tryparsamide and Amidines in pathogenic trypanosomes after treatment with \u201cMelarsen\u201d alone","volume":"167","author":"Rollo","year":"1951","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2017.09.067_bib19","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature10771","article-title":"High-throughput decoding of antitrypanosomal drug efficacy and resistance","volume":"482","author":"Alsford","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2017.09.067_bib20","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1146\/annurev.arplant.48.1.703","article-title":"Alternative oxidase: from gene to function","volume":"48","author":"Vanlerberghe","year":"1997","journal-title":"Annu. Rev. Plant Physiol. Plant Mol. Biol."},{"key":"10.1016\/j.ejmech.2017.09.067_bib21","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.1073\/pnas.1218386110","article-title":"Structure of the trypanosome cyanide-insensitive alternative oxidase","volume":"110","author":"Shiba","year":"2013","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.ejmech.2017.09.067_bib22","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0925-4439(02)00086-8","article-title":"Trypanosome alternative oxidase as a target of chemotherapy","volume":"1587","author":"Nihei","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ejmech.2017.09.067_bib23","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.bbabio.2009.12.021","article-title":"Purification and kinetic characterization of recombinant alternative oxidase from Trypanosoma brucei brucei","volume":"1797","author":"Kido","year":"2010","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"10.1016\/j.ejmech.2017.09.067_bib24","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1107\/S1744309109054062","article-title":"Crystallization and preliminary crystallographic analysis of cyanide-insensitive alternative oxidase from Trypanosoma brucei brucei","volume":"66","author":"Kido","year":"2010","journal-title":"Acta Crystallogr. Sect. F. Struct. Biol. Cryst. Commun."},{"key":"10.1016\/j.ejmech.2017.09.067_bib25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S1383-5769(98)00011-7","article-title":"Oral and intraperitoneal treatment of Trypanosoma brucei brucei with a combination of ascofuranone and glycerol in mice","volume":"47","author":"Yabu","year":"1998","journal-title":"Parasitol. Int."},{"key":"10.1016\/j.ejmech.2017.09.067_bib26","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1093\/jb\/mvs135","article-title":"Pharmacophore identification of ascofuranone, potent inhibitor of cyanide-insensitive alternative oxidase of Trypanosoma brucei","volume":"153","author":"Saimoto","year":"2013","journal-title":"J.\u00a0Biochem."},{"key":"10.1016\/j.ejmech.2017.09.067_bib27","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0166-6851(96)02797-1","article-title":"Erratum to \u201cAn antibiotic, ascofuranone, specifically inhibits respiration and in\u00a0vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei\u2019\u2019","volume":"84","author":"Minagawa","year":"1997","journal-title":"Mol. Biochem. Parasitol."},{"key":"10.1016\/j.ejmech.2017.09.067_bib28","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S1383-5769(03)00012-6","article-title":"The efficacy of ascofuranone in a consecutive treatment on Trypanosoma brucei brucei in mice","volume":"52","author":"Yabu","year":"2003","journal-title":"Parasitol. Int."},{"key":"10.1016\/j.ejmech.2017.09.067_bib29","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/S0040-4039(00)84326-9","article-title":"A\u00a0mild procedure for hydrolysis of alkoxymethyl aryl ethers to give hydroxyarenes. A rational synthesis of ascofuranone","volume":"27","author":"Saimoto","year":"1986","journal-title":"Tetrahedron Lett."},{"key":"10.1016\/j.ejmech.2017.09.067_bib30","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1016\/S0040-4020(01)96890-5","article-title":"Synthesis of (\u00b1)-ascochlorin, (\u00b1)-ascofuranone and LL-Z1272","volume":"40","author":"Mori","year":"1984","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ejmech.2017.09.067_bib31","doi-asserted-by":"crossref","first-page":"3795","DOI":"10.1016\/S0040-4039(01)91169-4","article-title":"A\u00a0simple total synthesis of (\u00b1)-ascofuranone","volume":"25","author":"Kau-Ming","year":"1984","journal-title":"Tetrahedron Lett."},{"key":"10.1016\/j.ejmech.2017.09.067_bib32","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0040-4039(00)84050-2","article-title":"A\u00a0general highly efficient access to prenylated phenolic natural products. Synthesis of colletochlorins B and D","volume":"27","author":"Saimoto","year":"1986","journal-title":"Tetrahedron Lett."},{"key":"10.1016\/j.ejmech.2017.09.067_bib33","doi-asserted-by":"crossref","first-page":"4725","DOI":"10.1016\/S0040-4039(97)00949-0","article-title":"The Florisil\u00ae catalyzed [1,3]-sigmatropic shift of allyl phenyl ethers \u2014 an entryway into novel mycophenolic acid analogues","volume":"38","author":"Talam\u00e1s","year":"1997","journal-title":"Tetrahedron Lett."},{"key":"10.1016\/j.ejmech.2017.09.067_bib34","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0014-5793(03)00120-0","article-title":"Purification of active recombinant trypanosome alternative oxidase","volume":"538","author":"Nihei","year":"2003","journal-title":"FEBS Lett."},{"key":"10.1016\/j.ejmech.2017.09.067_bib35","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1021\/jm000070g","article-title":"Anti-AIDS agents. 42. Synthesis and anti-HIV activity of disubstituted (3\u2018 R ,4\u2018 R )-3\u2018,4\u2018-Di- O -( S )-camphanoyl-(+)- cis -khellactone analogues","volume":"44","author":"Xie","year":"2001","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2017.09.067_bib36","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1021\/jo00221a009","article-title":"Total syntheses of fungal metabolites and functionalized furanones","volume":"50","author":"Chen","year":"1985","journal-title":"J.\u00a0Org. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352341730781X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352341730781X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,8,26]],"date-time":"2018-08-26T22:30:37Z","timestamp":1535322637000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S022352341730781X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":36,"alternative-id":["S022352341730781X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2017.09.067","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2017,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"African trypanosomiasis: Synthesis & SAR enabling novel drug discovery of ubiquinol mimics for trypanosome alternative oxidase","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2017.09.067","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}]}}