Toward G-Quadruplex-Based Anticancer Agents: Biophysical and Biological Studies of Novel AS1411 Derivatives

Autor: Emanuele Ugo Garzarella, Sonia Di Gaetano, Nunzia Iaccarino, Domenica Capasso, Anna M. Ogloblina, Marianna G. Yakubovskaya, Bruno Pagano, Nina G. Dolinnaya, Jussara Amato, Antonio Randazzo
Přispěvatelé: Ogloblina, Anna M, Iaccarino, Nunzia, Capasso, Domenica, Di Gaetano, Sonia, Garzarella, Emanuele U, Dolinnaya, Nina G, Yakubovskaya, Marianna G, Pagano, Bruno, Amato, Jussara, Randazzo, Antonio
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Circular dichroism
Magnetic Resonance Spectroscopy
Apoptosis
01 natural sciences
lcsh:Chemistry
Drug Stability
Fluorescence Resonance Energy Transfer
lcsh:QH301-705.5
Spectroscopy
chemistry.chemical_classification
Deoxyribonucleases
biology
G-quadruplex
Circular Dichroism
Nucleic Acid Heteroduplexes
RNA-Binding Proteins
General Medicine
Aptamers
Nucleotide
Computer Science Applications
Biochemistry
DNA Topoisomerases
Type I
Oligodeoxyribonucleotides
MCF-7 Cells
Female
in vitro biological assays
guanine-rich oligonucleotides
guanine-rich oligonucleotide
biophysical characterization
antiproliferative activity
Cancer therapy
Antineoplastic Agents
in vitro biological assay
010402 general chemistry
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
nucleolin
Humans
Physical and Theoretical Chemistry
Molecular Biology
Biological studies
Oligonucleotide
Topoisomerase
Organic Chemistry
Surface Plasmon Resonance
Phosphoproteins
0104 chemical sciences
030104 developmental biology
Enzyme
chemistry
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Drug Screening Assays
Antitumor
Topoisomerase I Inhibitors
Nucleolin
Thymine
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 7781, p 7781 (2020)
Volume 21
Issue 20
ISSN: 1422-0067
Popis: Certain G-quadruplex forming guanine-rich oligonucleotides (GROs), including AS1411, are endowed with cancer-selective antiproliferative activity. They are known to bind to nucleolin protein, resulting in the inhibition of nucleolin-mediated phenomena. However, multiple nucleolin-independent biological effects of GROs have also been reported, allowing them to be considered promising candidates for multi-targeted cancer therapy. Herein, with the aim of optimizing AS1411 structural features to find GROs with improved anticancer properties, we have studied a small library of AS1411 derivatives differing in the sequence length and base composition. The AS1411 derivatives were characterized by using circular dichroism and nuclear magnetic resonance spectroscopies and then investigated for their enzymatic resistance in serum and nuclear extract, as well as for their ability to bind nucleolin, inhibit topoisomerase I, and affect the viability of MCF-7 human breast adenocarcinoma cells. All derivatives showed higher thermal stability and inhibitory effect against topoisomerase I than AS1411. In addition, most of them showed an improved antiproliferative activity on MCF-7 cells compared to AS1411 despite a weaker binding to nucleolin. Our results support the hypothesis that the antiproliferative properties of GROs are due to multi-targeted effects.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje