Journalartikel

Jahr der Veröffentlichung: 2017

Seiten: 1471-1479

Zeitschrift: ChemMedChem

Bandnummer: 12

Heftnummer: 17

ISSN: 1860-7179

Open Access Status: Green

DOI Link: https://doi.org/10.1002/cmdc.201700368

Verlag: Wiley

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.

Harvard-Zitierstil: Sosic, 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-Zitierstil: Sosic, 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