Hybrid ligand–alkylating agents targeting telomeric G-quadruplex structures

Filippo Doria; Matteo Nadai; Marco Folini; Marco Di Antonio; Luca Germani; Claudia Percivalle; Claudia Sissi; Nadia Zaffaroni; Stefano Alcaro; Anna Artese; Sara N. Richter; Mauro Freccero

doi:10.1039/C2OB06816H

Hybrid ligand–alkylating agents targeting telomeric G-quadruplex structures†

Filippo Doria,^a Matteo Nadai,^b Marco Folini,^c Marco Di Antonio,^d Luca Germani,^a Claudia Percivalle,^a Claudia Sissi,^d Nadia Zaffaroni,^c Stefano Alcaro,^e Anna Artese,^e Sara N. Richter*^b and Mauro Freccero*^a

Author affiliations

* Corresponding authors

^a Dipartimento di Chimica, Università di Pavia, V.le Taramelli 10, 27100 Pavia, Italy
E-mail: mauro.freccero@unipv.it
Fax: +39 0382987323
Tel: +39 038298668

^b Dipartimento di Medicina Molecolare, Via Gabelli 63, Padova, Italy
E-mail: sara.richter@unipd.it

^c Dipartimento di Oncologia Sperimentale e Medicina Molecolare, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Amadeo 42, 20133 Milano, Italy

^d Department of Pharmaceutical and Pharmacological Sciences, Università di Padova, Via Marzolo 5, 35131 Padova, Italy

^e Dipartimento di Scienze della Salute, Università degli Studi “Magna Græcia” di Catanzaro, Campus Universitario “S. Venuta”, 88100 Catanzaro, Italy

Abstract

The synthesis, physico-chemical properties and biological effects of a new class of naphthalene diimides (NDIs) capable of reversibly binding telomeric DNA and alkylate it through an electrophilic quinone methide moiety (QM), are reported. FRET and circular dichroism assays showed a marked stabilization and selectivity towards telomeric G4 DNA folded in a hybrid topology. NDI–QMs’ alkylating properties revealed a good reactivity on single nucleosides and selectivity towards telomeric G4. A selected NDI was able to significantly impair the growth of melanoma cells by causing telomere dysfunction and down-regulation of telomerase expression. These findings points to our hybrid ligand–alkylating NDIs as possible tools for the development of novel targeted anticancer therapies.

Organic & Biomolecular Chemistry

Hybrid ligand–alkylating agents targeting telomeric G-quadruplex structures†

Abstract

Supplementary files

Article information

Download Citation

Permissions

Hybrid ligand–alkylating agents targeting telomeric G-quadruplex structures

Social activity

Search articles by author

Spotlight

Advertisements