{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:10:18Z","timestamp":1770970218914,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,3,8]],"date-time":"2017-03-08T00:00:00Z","timestamp":1488931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seventh Framework Programme","award":["603240"],"award-info":[{"award-number":["603240"]}]},{"name":"PRIN-2012","award":["201274BNKN_003"],"award-info":[{"award-number":["201274BNKN_003"]}]},{"name":"BioStruct-X","award":["283570"],"award-info":[{"award-number":["283570"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues (1\u20133) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes (Trypanosoma brucei PTR1\u2013TbPTR1 and Leishmania major\u2013LmPTR1) and parasites (Trypanosoma brucei and Leishmania infantum). A crystal structure of TbPTR1 in complex with compound 1 and the first crystal structures of LmPTR1-flavanone complexes (compounds 1 and 3) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants.<\/jats:p>","DOI":"10.3390\/molecules22030426","type":"journal-article","created":{"date-parts":[[2017,3,9]],"date-time":"2017-03-09T04:53:03Z","timestamp":1489035183000},"page":"426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity"],"prefix":"10.3390","volume":"22","author":[{"given":"Flavio","family":"Di Pisa","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6332-166X","authenticated-orcid":false,"given":"Giacomo","family":"Landi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}]},{"given":"Lucia","family":"Dello Iacono","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2574-3911","authenticated-orcid":false,"given":"Cecilia","family":"Pozzi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-8362","authenticated-orcid":false,"given":"Chiara","family":"Borsari","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1149-5953","authenticated-orcid":false,"given":"Stefania","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy"}]},{"given":"Matteo","family":"Santucci","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy"}]},{"given":"Nuno","family":"Santarem","sequence":"additional","affiliation":[{"name":"Institute for Molecular and Cell Biology, 4150-180 Porto, Portugal and Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto and Institute for Molecular and Cell Biology, 4150-180 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2392-6087","authenticated-orcid":false,"given":"Anabela","family":"Cordeiro-da-Silva","sequence":"additional","affiliation":[{"name":"Institute for Molecular and Cell Biology, 4150-180 Porto, Portugal and Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto and Institute for Molecular and Cell Biology, 4150-180 Porto, Portugal"}]},{"given":"Carolina","family":"Moraes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Nacional de Bioci\u00eancias (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas SP13083-100, Brazil"}]},{"given":"Laura","family":"Alcantara","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Nacional de Bioci\u00eancias (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas SP13083-100, Brazil"}]},{"given":"Vanessa","family":"Fontana","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Nacional de Bioci\u00eancias (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas SP13083-100, Brazil"}]},{"given":"Lucio","family":"Freitas-Junior","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Nacional de Bioci\u00eancias (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas SP13083-100, Brazil"},{"name":"GARDE, Instituto Butantan, S\u00e3o Paulo SP05503-900, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2543-1643","authenticated-orcid":false,"given":"Sheraz","family":"Gul","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, D-22525 Hamburg, Germany"}]},{"given":"Maria","family":"Kuzikov","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, D-22525 Hamburg, Germany"}]},{"given":"Birte","family":"Behrens","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, D-22525 Hamburg, Germany"}]},{"given":"Ina","family":"P\u00f6hner","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies, 69118 Heidelberg, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5951-8670","authenticated-orcid":false,"given":"Rebecca","family":"Wade","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies, 69118 Heidelberg, Germany"},{"name":"Center for Molecular Biology (ZMBH), DKFZ-ZMBH Alliance, Heidelberg University, 69120 Heidelberg, Germany"},{"name":"Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, 69120 Heidelberg, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0443-5402","authenticated-orcid":false,"given":"Maria","family":"Costi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, 41125 Modena, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4824-7478","authenticated-orcid":false,"given":"Stefano","family":"Mangani","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"},{"name":"Magnetic Resonance Center CERM, University of Florence, 50019 Sesto Fiorentino (FI), Italy"}]}],"member":"1968","published-online":{"date-parts":[[2017,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1517\/17460441.2011.585154","article-title":"X-ray crystallography: Assessment and validation of protein-small molecule complexes for drug discovery","volume":"6","author":"Cooper","year":"2011","journal-title":"Expert Opin. 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