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

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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. ORCID: https://orcid.org/0000-0003-4862-7999 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

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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,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups: Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021)
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Depositing User: LivePure Connector
Date Deposited: 31 Jul 2018 14:30
Last Modified: 25 Sep 2024 13:34
URI: https://ueaeprints.uea.ac.uk/id/eprint/67898
DOI: 10.1016/j.ejmech.2018.07.055

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