Journal article

Publication year: 2020

Pages: 2040-2051

Journal: ChemMedChem

Volume number: 15

Issue number: 21

ISSN: 1860-7179

Open access status: Hybrid

DOI Link: https://doi.org/10.1002/cmdc.202000457

Publisher: Wiley

Abstract: 
In this study, we describe the synthesis and biological evaluation of a set ofbis-3-chloropiperidines (B-CePs) containing rigid aromatic linker structures. A modification of the synthetic strategy also enabled the synthesis of a pilottris-3-chloropiperidine (Tri-CeP) bearing three reactivemeta-chloropiperidine moieties on the aromatic scaffold. A structure-reactivity relationship analysis of B-CePs suggests that the arrangement of the reactive units affects the DNA alkylating activity, while also revealing correlations between the electron density of the aromatic system and the reactivity with biologically relevant nucleophiles, both on isolated DNA and in cancer cells. Interestingly, all aromatic 3-chloropiperidines exhibited a marked cytotoxicity and tropism for 2D and 3D cultures of pancreatic cancer cells. Therefore, the new aromatic 3-chloropiperidines appear to be promising contenders for further development of mustard-based anticancer agents aimed at pancreatic cancers.

Harvard Citation style: Helbing, T., Carraro, C., Francke, A., Sosic, A., De Franco, M., Gandin, V., et al. (2020) Aromatic Linkers Unleash the Antiproliferative Potential of 3-Chloropiperidines Against Pancreatic Cancer Cells, ChemMedChem, 15(21), pp. 2040-2051. https://doi.org/10.1002/cmdc.202000457

APA Citation style: Helbing, T., Carraro, C., Francke, A., Sosic, A., De Franco, M., Gandin, V., Göttlich, R., & Gatto, B. (2020). Aromatic Linkers Unleash the Antiproliferative Potential of 3-Chloropiperidines Against Pancreatic Cancer Cells. ChemMedChem. 15(21), 2040-2051. https://doi.org/10.1002/cmdc.202000457