{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T09:38:04Z","timestamp":1786786684183,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T00:00:00Z","timestamp":1568592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013986","name":"Government of the United Kingdom","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013986","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>\n                    African trypanosomiasis, sleeping sickness in humans or nagana in animals, is a potentially fatal neglected tropical disease and a threat to 65 million human lives and 100 million small and large livestock animals in sub\u2010Saharan Africa. Available treatments for this devastating disease are few and have limited efficacy, prompting the search for new drug candidates. Simultaneous inhibition of the trypanosomal glycerol kinase (TGK) and trypanosom alalternative oxidase (TAO) is considered a validated strategy toward the development of new drugs. Our goal is to develop a TGK\u2010specific inhibitor for coadministration with ascofuranone (AF), the most potent TAO inhibitor. Here, we report on the identification of novel compounds with inhibitory potency against TGK. Importantly, one of these compounds (compound 17) and its derivatives (17a and 17b) killed trypanosomes even in the absence of AF. Inhibition kinetics revealed that derivative 17b is a mixed\u2010type and competitive inhibitor for TGK and TAO, respectively. Structural data revealed the molecular basis of this dual inhibitory action, which, in our opinion, will aid in the successful development of a promising drug to treat trypanosomiasis. Although the EC\n                    <jats:sub>50<\/jats:sub>\n                    of compound 17b against trypanosome cells was 1.77 \u03bcM, it had no effect on cultured human cells, even at 50 \u03bcM.\u2014Balogun, E. O., Inaoka, D. K., Shiba, T., Tsuge, C., May, B., Sato, T., Kido, Y., Nara, T., Aoki, T., Honma, T., Tanaka, A., Inoue, M., Matsuoka, S., Michels, P. A. M., Watanabe, Y.\u2010I., Moore, A. L., Harada, S., Kita, K. Discovery of trypanocidal coumarins with dual inhibition of both the glycerol kinase and alternative oxidase of\n                    <jats:italic>Trypanosoma brucei brucei<\/jats:italic>\n                    . FASEB J. 33, 13002\u201313013 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201901342r","type":"journal-article","created":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T18:20:22Z","timestamp":1568658022000},"page":"13002-13013","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Discovery of trypanocidal coumarins with dual inhibition of both the glycerol kinase and alternative oxidase of\n                    <i>Trypanosoma brucei brucei<\/i>"],"prefix":"10.1096","volume":"33","author":[{"given":"Emmanuel Oluwadare","family":"Balogun","sequence":"first","affiliation":[{"name":"Department of Biochemistry Ahmadu Bello University Zaria Nigeria"},{"name":"Department of Biomedical Chemistry Graduate School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Ken","family":"Inaoka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Ahmadu Bello University Zaria Nigeria"},{"name":"Department of Biomedical Chemistry Graduate School of Medicine"},{"name":"Department of Molecular Infection Dynamics, Shionogi Global Infectious Disease Division Institute of Tropical Medicine (NEKKEN), Nagasaki University Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoo","family":"Shiba","sequence":"additional","affiliation":[{"name":"Biochemistry and Medicine School of Life Sciences, University of Sussex Brighton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiaki","family":"Tsuge","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry Graduate School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"May","sequence":"additional","affiliation":[{"name":"Biochemistry and Medicine School of Life Sciences, University of Sussex Brighton United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Applied Biology Graduate School of Science and Technology, Kyoto Institute of Technology Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutoshi","family":"Kido","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Ahmadu Bello University Zaria Nigeria"},{"name":"Department of Parasitology Graduate School of Medicine, Osaka City University Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Nara","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Parasitology Juntendo University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Parasitology Juntendo University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruki","family":"Honma","sequence":"additional","affiliation":[{"name":"Systems and Structural Biology Center Riken Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Systems and Structural Biology Center Riken Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A. 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