Article In: orcid, cienciavitae
Screening of Scaffolds for the Design of G-Quadruplex Ligands
Applied Sciences
— 2022 — MDPI
Key information
Authors:
Published in
02/18/2022
Abstract
In the last decade, progress has been made in G-quadruplex (G4) ligands development, but for most compounds, the ligand binding mode is speculative or based on low resolution methods, with its discovery based on structure-based approaches. Herein, we report the synthesis of small (MW < 400 Da) heterocycle compounds, containing different aromatic scaffolds, such as phenyl, quinoline, naphthalene, phenanthroline and acridine moieties, in order to explore their stabilization effect towards different DNA G4s, such as those found in c-MYC, KRAS21 and VEGF promoters, 21G human telomeric motif and pre-MIR150. The fluorescence resonance energy transfer (FRET) melting assay indicates that the acridine moiety is the most active scaffold, followed by phenanthroline. The different scaffolds are promising in terms of drug-like properties and, in general, the IC50 values of the respective heterocycle compounds are lower in a cancer cell line, when compared with a normal cell line. The acridine derivative C5NH2 has the most favorable cytotoxic profile in terms of cell selectivity.
Publication details
Authors in the community:
António Manuel Rocha Paulo
ist126677
Publication version
AO - Author's Original
Publisher
MDPI
Link to the publisher's version
https://www.mdpi.com/journal/applsci
Title of the publication container
Applied Sciences
First page or article number
2170
Volume
12
Issue
4
ISSN
2076-3417
WoS (Web of Science)
Fields of Science and Technology (FOS)
health-sciences - Health sciences
Keywords
- G-quadruplex
- heterocycle compounds
- scaffolds
- drug-design
Publication language (ISO code)
eng - English
Alternative identifier (URI)
http://dx.doi.org/10.3390/app12042170
Rights type:
Open access
Creative Commons license
CC-BY - CC-BY