{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T08:22:34Z","timestamp":1768724554891,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006087","name":"General Direction of Academic Staff Affairs","doi-asserted-by":"publisher","award":["UNAM\u2010DGAPA\u2010PAPIIT IN215824"],"award-info":[{"award-number":["UNAM\u2010DGAPA\u2010PAPIIT IN215824"]}],"id":[{"id":"10.13039\/501100006087","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":[[2026,1]]},"abstract":"<jats:p>\n                    Lung cancer remains a leading cause of cancer\u2010related mortality worldwide, underscoring the need for novel therapeutic strategies. In this study, three hydroxamic acids derived from L\u2013cysteine are synthesized to explore their biological dual effect as Glyoxalase 1 (Glo\u20101) inhibitors and ferroptosis inducers. Among the synthesized derivates, compound\n                    <jats:bold>2<\/jats:bold>\n                    exhibited the highest inhibitory potency against Glo\u20101 and is the most potent compound against nonsmall cell lung cancer cell lines. For this compound, an increase in intracellular reactive oxygen species (ROS), depletion of intracellular reduced glutathione (GSH) levels, and induced morphological changes is observed that correspond to ferroptosis. Furthermore, these effects are reversed by Liproxstatin\u20101, a potent and selective ferroptosis inhibitor. Acute and subacute toxicological assays in mice showed mild toxicity (LD\n                    <jats:sub>50<\/jats:sub>\n                    \u2009&gt;\u20092000\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and moderate organ damage. These in\u2009vitro and in\u2009vivo findings suggest that ferroptosis induction may serve as a side effect of Glo\u20101 inhibition, making compound\n                    <jats:bold>2<\/jats:bold>\n                    a promising lead for further development and optimization.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500804","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T22:29:11Z","timestamp":1764541751000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glyoxalase\u20101 Inhibition Leads to Ferroptosis Induction in Lung Cancer Cells: A Dual Mechanism of Action of Hydroxamic Acids Derived from Cysteine"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6344-6291","authenticated-orcid":false,"given":"Josu\u00e9","family":"Mart\u00ednez\u2010Miranda","sequence":"first","affiliation":[{"name":"Departamento de Farmacia Facultad de Qu\u00edmica Universidad Nacional Aut\u00f3noma de M\u00e9xico  Avenue. Universidad 3000, C.U, Coyoac\u00e1n Mexico City 04510 M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7475-0969","authenticated-orcid":false,"given":"Dolores","family":"Aguilar\u2010C\u00e1zares","sequence":"additional","affiliation":[{"name":"Laboratorio de Cancer Pulmonar Departamento de Enfermedades Cronico\u2010Degenerativas Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas  Mexico City 14080 Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3431-3879","authenticated-orcid":false,"given":"Ang\u00e9lica","family":"Flores\u2013Flores","sequence":"additional","affiliation":[{"name":"Departamento de Inmunofarmacologia Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas  Mexico City 14080 Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel \u00c1ngel","family":"Santos\u2010Contreras","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia Facultad de Qu\u00edmica Universidad Nacional Aut\u00f3noma de M\u00e9xico  Avenue. Universidad 3000, C.U, Coyoac\u00e1n Mexico City 04510 M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0746-2286","authenticated-orcid":false,"given":"Jos\u00e9 S.","family":"L\u00f3pez\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Cancer Pulmonar Departamento de Enfermedades Cronico\u2010Degenerativas Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas  Mexico City 14080 Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9455-5397","authenticated-orcid":false,"given":"Rodrigo","family":"Aguayo\u2010Ortiz","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia Facultad de Qu\u00edmica Universidad Nacional Aut\u00f3noma de M\u00e9xico  Avenue. Universidad 3000, C.U, Coyoac\u00e1n Mexico City 04510 M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1292-3833","authenticated-orcid":false,"given":"Rog\u00e9lio","family":"Hern\u00e1ndez\u2010Pando","sequence":"additional","affiliation":[{"name":"Departamento de Patolog\u00eda Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n  Mexico City 1408 Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8724-9495","authenticated-orcid":false,"given":"Francisco","family":"Hern\u00e1ndez\u2010Luis","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia Facultad de Qu\u00edmica Universidad Nacional Aut\u00f3noma de M\u00e9xico  Avenue. Universidad 3000, C.U, Coyoac\u00e1n Mexico City 04510 M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Global Cancer Facts & Figures 5th edition","year":"2024"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110663"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.05.006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-12119-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-818606-0.00036-5"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2015.1121346"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi990696c"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0361045"},{"key":"e_1_2_9_11_1","first-page":"15","volume-title":"Oxidative Stress\u2010Molecular Mechanisms and Biological Effects","author":"Semchyshyn H. M.","year":"2012"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2020.02.015"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(86)90561-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01165-z"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-023-00427-w"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2016.572"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28159"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules171213740"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14344"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S110997"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-990803"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c03628"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.05.046"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/19768354.2012.696554"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201500486"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4792"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3943"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.0c00121"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1493"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758\u20102946\u20103\u201033"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00255"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10262"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.1c00645"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500804","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202500804","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T17:09:31Z","timestamp":1768669771000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202500804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,30]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/cmdc.202500804"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202500804","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,30]]},"assertion":[{"value":"2025-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500804"}}