Journal article

Direct and Topoisomerase II Mediated DNA Damage by Bis‐3‐chloropiperidines: The Importance of Being an Earnest G


Authors listSosic, A; Zuravka, I; Schmitt, N-K; Miola, A; Göttlich, R; Fabris, D; Gatto, B

Publication year2017

Pages1471-1479

JournalChemMedChem

Volume number12

Issue number17

ISSN1860-7179

Open access statusGreen

DOI Linkhttps://doi.org/10.1002/cmdc.201700368

PublisherWiley


Abstract

Bis‐3‐chloropiperidines are a new class of DNA‐active compounds capable
of alkylating nucleobases and inducing strand cleavage. In this study,
we investigated the reactivity of these mustard‐based agents with both
single‐ and double‐stranded DNA constructs. Polyacrylamide gel
electrophoresis (PAGE) and electrospray ionization mass spectrometry
(ESI‐MS) were used to obtain valuable insight into their mechanism at
the molecular level and to investigate their time‐ and
concentration‐dependent activity. The results revealed the preferential
formation of mono‐ and bifunctional adducts at nucleophilic guanine
sites. In a stepwise fashion, alkylation was followed by depurination
and subsequent strand scission at the ensuing apurinic site. We
demonstrated that the covalent modifications introduced by this new
class of compounds can inhibit the activity of essential DNA‐processing
proteins, such as topoisomerase IIα, thereby suggesting that
bis‐3‐chloropiperidines may have excellent anticancer potential.




Citation Styles

Harvard Citation styleSosic, A., Zuravka, I., Schmitt, N., Miola, A., Göttlich, R., Fabris, D., et al. (2017) Direct and Topoisomerase II Mediated DNA Damage by Bis‐3‐chloropiperidines: The Importance of Being an Earnest G, ChemMedChem, 12(17), pp. 1471-1479. https://doi.org/10.1002/cmdc.201700368

APA Citation styleSosic, A., Zuravka, I., Schmitt, N., Miola, A., Göttlich, R., Fabris, D., & Gatto, B. (2017). Direct and Topoisomerase II Mediated DNA Damage by Bis‐3‐chloropiperidines: The Importance of Being an Earnest G. ChemMedChem. 12(17), 1471-1479. https://doi.org/10.1002/cmdc.201700368


Last updated on 2025-10-06 at 10:48