β-amino alcohols and their respective 2-phenyl-N-alkyl aziridines as potential DNA minor groove binders

Vaidergorn, Miguel M., Carneiro, Zumira A., Lopes, Carla D., de Albuquerque, Sérgio, Reis, Felipe C.C., Nikolaou, Sofia, Mello, Juliana F.R., Genesi, Giovani L., Trossini, Gustavo H.G., Ganesan, A. and Emery, Flavio S. (2018) β-amino alcohols and their respective 2-phenyl-N-alkyl aziridines as potential DNA minor groove binders. European Journal of Medicinal Chemistry, 157. pp. 657-664. ISSN 0223-5234

[img]
Preview
PDF (Accepted manuscript) - Submitted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (1MB) | Preview

Abstract

It is known that aziridines and nitrogen mustards exert their biological activities, especially in chemotherapy, via DNA alkylation. The studied scaffold, 2-phenyl-1-aziridine, provides a distinct conformation compared to commonly used aziridines, and therefore, leads to a change in high-strained ring reactivity towards biological nucleophiles, such as DNA. The above series of compounds was tested in three breast cell lines: MCF-10, a healthy cell; MCF-7, a hormone responsive cancer cell; and MDA-MB-231, a triple negative breast cancer cell. Both aziridines and their precursors, β-amino alcohols, showed activity towards these cells, and some of the compounds showed higher selectivity index than cisplatin, the drug used as control. When the type of cell death was investigated, the synthesized compounds demonstrated higher apoptosis and lower necrosis rates than cisplatin, and when the mechanism of action was studied, the compounds were shown to interact with DNA via its minor groove instead of alkylation or intercalation.

Item Type: Article
Uncontrolled Keywords: aziridines,triple negative breast cancer,minor groove binding,β-amino alcohols
Faculty \ School: Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 31 Jul 2018 14:30
Last Modified: 07 Nov 2020 00:55
URI: https://ueaeprints.uea.ac.uk/id/eprint/67898
DOI: 10.1016/j.ejmech.2018.07.055

Actions (login required)

View Item View Item