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Appended Aromatic Moieties in Flexible Bis‐3‐chloropiperidines Confer Tropism against Pancreatic Cancer Cells
Author(s) -
Carraro Caterina,
Helbing Tim,
Francke Alexander,
Zuravka Ivonne,
Sosic Alice,
De Franco Michele,
Gandin Valentina,
Gatto Barbara,
Göttlich D. Richard
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000814
Subject(s) - linker , tropism , reactivity (psychology) , pancreatic cancer , chemistry , selectivity , dna , combinatorial chemistry , cytotoxicity , stereochemistry , cancer research , biochemistry , biology , cancer , in vitro , medicine , immunology , genetics , catalysis , virus , alternative medicine , pathology , computer science , operating system
Nitrogen mustards (NMs) are an old but still largely diffused class of anticancer drugs. However, spreading mechanisms of resistance undermine their efficacy and therapeutic applicability. To expand their antitumour value, we developed bis‐3‐chloropiperidines (B‐CePs), a new class of mustard‐based alkylating agent, and we recently reported the striking selectivity for BxPC‐3 pancreatic tumour cells of B‐CePs bearing aromatic moieties embedded in the linker. In this study, we demonstrate that such tropism is shared by bis‐3‐chloropiperidines bearing appended aromatic groups in flexible linkers, whereas esters substituted by aliphatic groups or by efficient DNA‐interacting 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‐3‐chloropiperidines. Together, these findings support the exploitation of B‐CePs as potential antitumour clinical candidates.