{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:04:29Z","timestamp":1791925469884,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100018776","name":"Cancer Center, University of Florida Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018776","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","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":[[2022,4,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lung cancer is the leading cause of cancer\u2010related deaths and chemoprevention should be developed. We recently identified dihydromethysticin (DHM) as a promising candidate to prevent NNK\u2010induced lung tumorigenesis. To probe its mechanisms and facilitate its future translation, we investigated the structure\u2010activity relationship of DHM on NNK\u2010induced DNA damage in A\/J mice. Twenty DHM analogs were designed and synthesized. Their activity in reducing NNK\u2010induced DNA damage in the target lung tissues was evaluated. The unnatural enantiomer of DHM was identified to be more potent than the natural enantiomer. The methylenedioxy functional moiety did not tolerate modifications while the other functional groups (the lactone ring and the ethyl linker) accommodated various modifications. Importantly, analogs of high structural similarity to DHM with distinct efficacy in reducing NNK\u2010induced DNA damage have been identified. They will serve as chemical probes to elucidate the mechanisms of DHM in blocking NNK\u2010induced lung carcinogenesis.<\/jats:p>","DOI":"10.1002\/cmdc.202100727","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T22:09:03Z","timestamp":1642802943000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<i>In vivo<\/i> Structure\u2010Activity Relationship of Dihydromethysticin in Reducing Nicotine\u2010Derived Nitrosamine Ketone (NNK)\u2010Induced Lung DNA Damage against Lung Carcinogenesis in A\/J Mice"],"prefix":"10.1002","volume":"17","author":[{"given":"Santanu","family":"Hati","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry University of Florida  1345 Center Drive Gainesville FL 32610 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry University of Florida  1345 Center Drive Gainesville FL 32610 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Florida  Gainesville FL 32610 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Pennsylvania State University  Hershey PA 17033 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4266-6236","authenticated-orcid":false,"given":"Chengguo","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry University of Florida  1345 Center Drive Gainesville FL 32610 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/jsc.2016.11"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2016.11.002"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12819"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2008.05.010"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-08-0027"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X11009202"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-13-0301"},{"key":"e_1_2_8_9_1","unstructured":"WHO Food and Agriculture Organization of the United Nations2016 1 1."},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hup.2725"},{"key":"e_1_2_8_11_1","first-page":"96","volume":"8","author":"Balick M. J.","year":"2002","journal-title":"Altern. Ther. Health Med."},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.1988.tb93809.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2014.11.012"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.4652"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e3283036768"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.07.093"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2011.01.018"},{"key":"e_1_2_8_18_1","unstructured":"WHO WHO Document Production Service2007."},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2003.07.005"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(03)00175-2"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12103044"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgu149"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx980005y"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.0c00161"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00921"},{"key":"e_1_2_8_26_1","first-page":"2894","volume":"49","author":"Morse M. A.","year":"1989","journal-title":"Cancer Res."},{"key":"e_1_2_8_27_1","first-page":"2613","volume":"50","author":"Morse M. A.","year":"1990","journal-title":"Cancer Res."},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3998\/ark.5550190.0013.813"},{"key":"e_1_2_8_29_1","author":"Hu Q.","year":"2021","journal-title":"Carcinogenesis"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197940"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202100727","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202100727","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202100727","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T12:07:04Z","timestamp":1760270824000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202100727"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,4]]},"references-count":30,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,4,5]]}},"alternative-id":["10.1002\/cmdc.202100727"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202100727","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,4]]},"assertion":[{"value":"2021-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202100727"}}