{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T04:55:25Z","timestamp":1769835325229,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Twenty\u2010two quaternary 8\u2010dichloromethylprotoberberine alkaloids were synthesized from unmodified quaternary protoberberine alkaloids (QPAs) to improve their physical and chemical properties and to obtain selectively anticancer derivatives. The synthesized derivatives showed more appropriate octanol\/water partition coefficients by up to values 3\u20134 compared to unmodified QPA substrates. In addition, these compounds exhibited significant antiproliferative activity against colorectal cancer cells and lower toxicity on normal cells, resulting in more significant selectivity indices than unmodified QPA compounds <jats:italic>in\u2005vitro<\/jats:italic>. The IC<jats:sub>50<\/jats:sub> values of antiproliferative activity of quaternary 8\u2010dichloromethyl\u2010pseudoberberine 4\u2010chlorobenzenesulfonate and quaternary 8\u2010dichloromethyl\u2010pseudopalmatine methanesulfonate against colorectal cancer cells are 0.31\u2005\u03bcM and 0.41\u2005\u03bcM, respectively, significantly stronger than those of other compounds and positive control 5\u2010fluorouracil. These findings suggest that 8\u2010dichloromethylation can be used as one of the modification strategies to guide the structural modification and subsequent investigation of anticancer drugs for CRC based on QPAs.<\/jats:p>","DOI":"10.1002\/cbdv.202300570","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T04:34:56Z","timestamp":1684298096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis and Cytotoxicity Assessment against Human Colorectal Cancer Cell Lines of Quaternary 8\u2010Dichloromethyl Protoberberine Alkaloids"],"prefix":"10.1002","volume":"20","author":[{"given":"Ling\u2010Wen","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue\u2010Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi\u2010Hong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An\u2010Jun","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6721-1409","authenticated-orcid":false,"given":"Hai\u2010Lin","family":"Qin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 100050 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,6]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32319-0"},{"key":"e_1_2_9_2_1","unstructured":"J. Ferlay M. Colombet I. Soerjomataram D.\u2005M. Parkin M. Pineros A. Znaor F. Bray Int. J. Cancer2021."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.12.019"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djz093"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01624"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00964"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7032"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.30787"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1135"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b01346"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18414-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.125"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2020.06.014"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.113776"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30430-3"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22179"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.296"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/np000554f"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25081871"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/10286020.2021.1935895"},{"key":"e_1_2_9_21_1","unstructured":"H.\u2005L. Qin L.\u2005Q. Wu X. Li H.\u2005J. Zhang L. Song A.\u2005J. Deng X.\u2005N. Tang Z.\u2005H. Zhang Z.\u2005H. Li PCT\/CN2019\/082701."},{"key":"e_1_2_9_22_1","first-page":"370","volume":"25","author":"Li J.","year":"2017","journal-title":"Chin. J. Med. Chem."},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.104994"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00128"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(98)00090-8"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2022.121587"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24010103"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2018.07.051"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2017.05.081"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.29.883"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202300570","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T08:28:17Z","timestamp":1695803297000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.202300570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/cbdv.202300570"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.202300570","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6]]},"assertion":[{"value":"2023-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202300570"}}