Journal article

Publication year: 2019

Pages: 552-557

Journal: ACS Medicinal Chemistry Letters

Volume number: 10

Issue number: 4

ISSN: 1948-5875

Open access status: Green

DOI Link: https://doi.org/10.1021/acsmedchemlett.8b00580

Publisher: American Chemical Society

Abstract: 
The pressing demand for sustainable antitumor drugs prompted us to investigate 3-chloropiperidines as potential mustard-based anticancer agents. In this study, an explorative set of variously decorated monofunctional 3-chloropiperidines (M-CePs) was efficiently synthesized through a fast and affordable route providing high yields of pure racemates and enantiomers. Consistently with their reactivity, M-CePs were demonstrated to alkylate DNA in vitro. On a panel of carcinoma cell lines, M-CePs exhibited low nanomolar cytotoxicity indexes, which showed their remarkable activity against pancreatic cancer cells and in all cases performed strikingly better than the chlorambucil control. Very interestingly, stereochemistry modulated the activity of M-CePs in unexpected ways, pointing to additional molecular mechanisms of action beyond the direct damage of genomic DNA. This encouraging combination of efficacy and sustainability suggests they are valid candidates for anticancer agent development.

Harvard Citation style: Carraro, C., Francke, A., Sosic, A., Kohl, F., Helbing, T., De Franco, M., et al. (2019) Behind the Mirror: Chirality Tunes the Reactivity and Cytotoxicity of Chloropiperidines as Potential Anticancer Agents, ACS Medicinal Chemistry Letters, 10(4), pp. 552-557. https://doi.org/10.1021/acsmedchemlett.8b00580

APA Citation style: Carraro, C., Francke, A., Sosic, A., Kohl, F., Helbing, T., De Franco, M., Fabris, D., Göttlich, R., & Gatto, B. (2019). Behind the Mirror: Chirality Tunes the Reactivity and Cytotoxicity of Chloropiperidines as Potential Anticancer Agents. ACS Medicinal Chemistry Letters. 10(4), 552-557. https://doi.org/10.1021/acsmedchemlett.8b00580