{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T01:18:52Z","timestamp":1784423932756,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T00:00:00Z","timestamp":1607212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In previous studies, we demonstrated that esters of bendamustine containing a basic moiety are far more cytotoxic anticancer agents than their parent compound and that the substitution of the labile ester moiety by a branched ester or an amide markedly increases stability in the blood plasma. In the current study, we showed that this substitution was bioisosteric. Aiming at increased cytotoxicity, we introduced the same modification to related nitrogen mustards: 6\u2010isobendamustine, chlorambucil, and melphalan. The synthesis was accomplished using the coupling reagents <jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2032\u2010dicyclohexylcarbodiimide or 2\u2010(1<jats:italic>H<\/jats:italic>\u2010benzotriazole\u20101\u2010yl)\u20101,1,3,3\u2010tetramethylaminium tetrafluoroborate. Cytotoxicity against a panel of diverse cancer cells (carcinoma, sarcoma, and malignant melanoma) was assessed in a kinetic chemosensitivity assay. The target compounds showed cytotoxic or cytocidal effects at concentrations above 1\u2009\u00b5M: a striking enhancement over bendamustine and 6\u2010isobendamustine, both ineffective against the selected cancer cells at concentrations up to 50\u2009\u00b5M, and a considerable improvement over chlorambucil, showing some potency only against the sarcoma cells. Melphalan was almost as effective as the target compounds\u2014derivatization only provided a small improvement. The novel cytostatics are of interest as model compounds for analyzing a correlation between cytotoxicity and membrane transport and for the treatment of malignancies.<\/jats:p>","DOI":"10.1002\/ardp.202000366","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T07:39:10Z","timestamp":1607326750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Derivatives of nitrogen mustard anticancer agents with improved cytotoxicity"],"prefix":"10.1002","volume":"354","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8382-6315","authenticated-orcid":false,"given":"Frauke","family":"Antoni","sequence":"first","affiliation":[{"name":"Institute of Pharmacy University of Regensburg Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6491-9874","authenticated-orcid":false,"given":"G\u00fcnther","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy University of Regensburg Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2017.02.75"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1529"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc706"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.103.2675.409"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.04.001"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/jr9530002386"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1587"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00578555"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00114971"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2014.05.015"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/jr9540002409"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(79)90217-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082373"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02493133"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2012.08.011"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/prac.19630200310"},{"issue":"10","key":"e_1_2_9_18_1","first-page":"1013","volume":"110","author":"Ozegowski W.","year":"1971","journal-title":"Zbl. Pharm"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24057"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2011.03.002"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1061"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2011.03.003"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.18.7252"},{"key":"e_1_2_9_24_1","unstructured":"J.Colledge (Astellas Deutschland GmbH) Germany WO2010063493A1 2010."},{"key":"e_1_2_9_25_1","unstructured":"R. Y.LaBell P. R.Patel (Cephalon Inc.) USA US20120157505A1 2012."},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2008.09.001"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc900453f"},{"key":"e_1_2_9_28_1","unstructured":"R. P.Bakale P. D.Brown J.Chen A. S.Drager R. Y.LaBell R. E.McKean P. R.Patel R. C.Roemmele (Cephalon Inc.) USA WO2014075035A1 \u00a02015."},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0133743"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2014.11.038"},{"key":"e_1_2_9_31_1","unstructured":"H.Schickaneder C.Schickaneder A.Buschauer G.Bernhardt S.Huber M.Limmert M.Lubbe H.Hofmeier WO189847A1 \u00a02013."},{"key":"e_1_2_9_32_1","unstructured":"H.Schickaneder C.Schickaneder A.Buschauer G.Bernhardt S.Huber F.Antoni WO091827A1 \u00a02015."},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008390-200410000-00004"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01192309"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00143a009"},{"key":"e_1_2_9_36_1","unstructured":"B. E.Toki P. D.Senter (Seattle Genetics Inc.) USA WO070457A1 \u00a02005."}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202000366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.202000366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202000366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T04:04:14Z","timestamp":1693541054000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.202000366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,6]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1002\/ardp.202000366"],"URL":"https:\/\/doi.org\/10.1002\/ardp.202000366","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,6]]},"assertion":[{"value":"2020-09-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2000366"}}