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To expand their antitumour value, we developed bis\u20103\u2010chloropiperidines (B\u2010CePs), a new class of mustard\u2010based alkylating agent, and we recently reported the striking selectivity for BxPC\u20103 pancreatic tumour cells of B\u2010CePs bearing aromatic moieties <jats:italic>embedded<\/jats:italic> in the linker. In this study, we demonstrate that such tropism is shared by bis\u20103\u2010chloropiperidines bearing <jats:italic>appended<\/jats:italic> aromatic groups in flexible linkers, whereas esters substituted by aliphatic groups or by efficient DNA\u2010interacting groups are potent but nonselective cytotoxic agents. Besides, we describe how the critical balance between water stability and DNA reactivity can affect the properties of bis\u20103\u2010chloropiperidines. Together, these findings support the exploitation of B\u2010CePs as potential antitumour clinical candidates.<\/jats:p>","DOI":"10.1002\/cmdc.202000814","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T04:39:26Z","timestamp":1605587966000},"page":"860-868","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Appended Aromatic Moieties in Flexible Bis\u20103\u2010chloropiperidines Confer Tropism against Pancreatic Cancer Cells"],"prefix":"10.1002","volume":"16","author":[{"given":"Caterina","family":"Carraro","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padova  Via Francesco Marzolo 5 35131 Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Helbing","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry Justus Liebig University Giessen  Heinrich-Buff-Ring 17 35392 Giessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Francke","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry Justus Liebig University Giessen  Heinrich-Buff-Ring 17 35392 Giessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivonne","family":"Zuravka","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry Justus Liebig University Giessen  Heinrich-Buff-Ring 17 35392 Giessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Sosic","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padova  Via Francesco Marzolo 5 35131 Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"De Franco","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padova  Via Francesco Marzolo 5 35131 Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Gandin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padova  Via Francesco Marzolo 5 35131 Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Gatto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Padova  Via Francesco Marzolo 5 35131 Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1424-3084","authenticated-orcid":false,"given":"D. 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