Journal article

Publication year: 2021

Pages: 860-868

Journal: ChemMedChem

Volume number: 16

Issue number: 5

ISSN: 1860-7179

eISSN: 1860-7187

Open access status: Hybrid

DOI Link: https://doi.org/10.1002/cmdc.202000814

Publisher: Wiley

Abstract: 

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.

Harvard Citation style: Carraro, C., Helbing, T., Francke, A., Zuravka, I., Sosic, A., De Franco, M., et al. (2021) Appended Aromatic Moieties in Flexible Bis-3-chloropiperidines Confer Tropism against Pancreatic Cancer Cells, ChemMedChem, 16(5), pp. 860-868. https://doi.org/10.1002/cmdc.202000814

APA Citation style: Carraro, C., Helbing, T., Francke, A., Zuravka, I., Sosic, A., De Franco, M., Gandin, V., Gatto, B., & Göttlich, R. (2021). Appended Aromatic Moieties in Flexible Bis-3-chloropiperidines Confer Tropism against Pancreatic Cancer Cells. ChemMedChem. 16(5), 860-868. https://doi.org/10.1002/cmdc.202000814