{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:16:26Z","timestamp":1777860986853,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006049","name":"Sectoral Commission for Scientific Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,4,28]]},"abstract":"<jats:p>\n                    Chagas disease and leishmaniasis are neglected protozoan diseases recognized by the World Health Organization as major public health problems. These diseases affect millions of people worldwide, yet effective treatments remain unavailable. Triosephosphate isomerase (TIM), a glycolytic enzyme that exhibits high catalytic efficiency for the isomerization of glyceraldehyde\u20103\u2010phosphate and dihydroxyacetone\u2010phosphate exclusively in its dimeric form, was subjected to virtual screening. Using a deep neural network for structure\u2010based drug design that predicts binding affinity between small molecules and proteins of known structure, 12.5 million commercially available compounds were screened. From this, 82 compounds were selected for in vitro evaluation. Six compounds inhibited TIM from\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    , three of which exhibited anti\u2010T. cruzi activity. Eight compounds demonstrated activity against the parasites\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    and\n                    <jats:italic>Leishmania infantum<\/jats:italic>\n                    . Two compounds showed similar potency against both parasites: 3\u2010(1\u2010acetyl\u20105\u2010(4\u2010bromophenyl)\u22124,5\u2010dihydro\u20101H\u2010pyrazol\u20103\u2010yl)\u20104\u2010hydroxy\u20106\u2010methyl\u20102H\u2010pyran\u20102\u2010one (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200916 \u00b1 3\u2009\u03bcM) and 3\u2010[(4\u2010bromophenyl)sulfanyl]\u20101\u2010(3\u2010nitrophenyl)propan\u20101\u2010one (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200912 \u00b1 1\u2009\u03bcM). These compounds exhibit favorable selectivity and toxicological profiles, as well as in vivo activity, indicating their potential for future drug development.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500896","type":"journal-article","created":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T06:39:26Z","timestamp":1777185566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Triose Phosphate Isomerase Inhibitor With Dual Trypanosomicidal Activity was Identified Using Artificial Intelligence\u2010Based Virtual Screening"],"prefix":"10.1002","volume":"21","author":[{"given":"Elena","family":"Aguilera","sequence":"first","affiliation":[{"name":"Grupo de Qu\u00edmica Org\u00e1nica Medicinal Instituto de Qu\u00edmica Biol\u00f3gica Facultad de Ciencias Universidad de la Rep\u00fablica  Montevideo Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Ramos","sequence":"additional","affiliation":[{"name":"Laboratorio de Mol\u00e9culas Bioactivas Departamento de Ciencias Biol\u00f3gicas CENUR Litoral Norte Universidad de la Rep\u00fablica  Paysand\u00fa Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aram","family":"Davtyan","sequence":"additional","affiliation":[{"name":"Scientific staff Atomwise Inc.  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nallely","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Estructural Instituto de Fisiolog\u00eda Celular Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruy","family":"Perez\u2010Montfort","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Estructural Instituto de Fisiolog\u00eda Celular Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elva","family":"Serna","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Tropical Instituto de Investigaciones en Ciencias de la Salud Universidad Nacional de Asunci\u00f3n  San Lorenzo Paraguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Yaluff","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Tropical Instituto de Investigaciones en Ciencias de la Salud Universidad Nacional de Asunci\u00f3n  San Lorenzo Paraguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-6100","authenticated-orcid":false,"given":"Guzm\u00e1n","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Laboratorio de Mol\u00e9culas Bioactivas Departamento de Ciencias Biol\u00f3gicas CENUR Litoral Norte Universidad de la Rep\u00fablica  Paysand\u00fa Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,25]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"World Health Organization Chagas Disease (2024). Accessed 13 February 2025. (https:\/\/www.who.int\/n%0Aews\u2010room\/fact\u2010sheets\/detail\/chagas\u2010disease\u2010(american\u2010trypanosomiasis."},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.06.040"},{"key":"e_1_2_12_4_1","unstructured":"World Health Organization Leishmaniasis 2024. Accessed 13 February 2025. (https:\/\/www.who.int\/n%0Aews\u2010room\/fact\u2010sheets\/detail\/chagas\u2010disease\u2010(american\u2010trypanosomiasis."},{"key":"e_1_2_12_5_1","first-page":"100","article-title":"Leishmaniosis Visceral: A. 101 a\u00f1os Del Primer Caso Diagnosticado en Las Am\u00e9ricas Visceral Leishmaniosis: 101 Years from the First Case Diagnosed in the Americas","volume":"10","author":"Oddone Costanzo R.","year":"2012","journal-title":"Memorias del Instituto de Investigaciones en Ciencias de la Salud"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00687-4"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2024.2349155"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmacy12010030"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/0113894501298864240627060247"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2024-098079"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0013522"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-052897"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760240183"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1718438"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2025.02.004"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.48550\/ARXIV.1510.02855"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c01250"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2010.09.034"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1515\/jib-2018-0065"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-54655-z"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm301008n"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901137j"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci9803381"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22050709"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201500385"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24203800"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500896","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202500896","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500896","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:38:12Z","timestamp":1777516692000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202500896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,25]]},"references-count":25,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,4,28]]}},"alternative-id":["10.1002\/cmdc.202500896"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202500896","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,25]]},"assertion":[{"value":"2025-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500896"}}