{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T08:11:21Z","timestamp":1778141481293,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"NSERC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","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":[[2026,3,13]]},"abstract":"<jats:p>\n                    Lapachol is a natural product with antimicrobial activity. Though promising for combating antimicrobial resistance, lapachol has toxicity to mammalian cells, which will cause severe side effects in vivo. To mitigate this, we developed alapachol prodrug which is dependent on the action of nitroreductase\u2014an enzyme expressed in bacteria but not healthy mammalian cells. We observed release of lapachol in vitro by purified nitroreductase and in the gram\u2010positive bacterial strain,\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    . Colony formation assays in\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    indicated release of lapachol, achieving comparable levels of toxicity as free lapachol. Lastly, minimal toxicity of our prodrug was observed in mammalian cell culture, demonstrating a\u2009&gt;10\u2010fold selectivity for bacteria over healthy mammalian cells.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500997","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:39:07Z","timestamp":1773427147000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Nitroreductase\u2010Activatable Lapachol Against\n                    <i>Bacillus subtilis<\/i>\n                    Unveils Antimicrobial Specificity"],"prefix":"10.1002","volume":"21","author":[{"given":"Ivonne R.","family":"Lopez\u2010Miranda","sequence":"first","affiliation":[{"name":"Department of Chemical &amp; Physical Sciences University of Toronto Mississauga  Mississauga Canada"},{"name":"Department of Chemistry University of Toronto  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianyi","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Physical Sciences University of Toronto Mississauga  Mississauga Canada"},{"name":"Department of Physics University of Toronto Toronto  Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2515-4025","authenticated-orcid":false,"given":"Joshua N.","family":"Milstein","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Physical Sciences University of Toronto Mississauga  Mississauga Canada"},{"name":"Department of Physics University of Toronto Toronto  Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1505-2375","authenticated-orcid":false,"given":"Andrew A.","family":"Beharry","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Physical Sciences University of Toronto Mississauga  Mississauga Canada"},{"name":"Department of Chemistry University of Toronto  Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2019.10.008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24655"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)02724\u20100"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006055"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2007.02.005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3998\/ark.5550190.0008.204"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-43044-9.00115-1"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c00398"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cptc.202400164"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574\u20106976.2008.00107.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00047a002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.02.049"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4MD00890A"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1691\/ph.2007.7.6757"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20102006\u2010959504"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201403064"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1382\u20106689(97)00019\u20107"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e22575"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac497"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500997","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202500997","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500997","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T07:19:43Z","timestamp":1778138383000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202500997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,3,13]]}},"alternative-id":["10.1002\/cmdc.202500997"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202500997","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]},"assertion":[{"value":"2025-11-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500997"}}