Antiproliferative Properties and G-Quadruplex-Binding of Symmetrical Naphtho[1,2-b:8,7-b']dithiophene Derivatives.
Molecules
; 26(14)2021 Jul 16.
Article
em En
| MEDLINE
| ID: mdl-34299583
ABSTRACT
Background:
G-quadruplex (G4) forming sequences are recurrent in telomeres and promoter regions of several protooncogenes. In normal cells, the transient arrangements of DNA in G-tetrads may regulate replication, transcription, and translation processes. Tumors are characterized by uncontrolled cell growth and tissue invasiveness and some of them are possibly mediated by gene expression involving G-quadruplexes. The stabilization of G-quadruplex sequences with small molecules is considered a promising strategy in anticancer targeted therapy.Methods:
Molecular virtual screening allowed us identifying novel symmetric bifunctionalized naphtho[1,2-b8,7-b']dithiophene ligands as interesting candidates targeting h-Telo and c-MYC G-quadruplexes. A set of unexplored naphtho-dithiophene derivatives has been synthesized and biologically tested through in vitro antiproliferative assays and spectroscopic experiments in solution.Results:
The analysis of biological and spectroscopic data highlighted noteworthy cytotoxic effects on HeLa cancer cell line (GI50 in the low µM range), but weak interactions with G-quadruplex c-MYC promoter.Conclusions:
The new series of naphtho[1,2-b8,7-b']dithiophene derivatives, bearing the pharmacophoric assumptions necessary to stabilize G-quadruplexes, have been designed and successfully synthesized. The interesting antiproliferative results supported by computer aided rational approaches suggest that these studies are a significant starting point for a lead optimization process and the isolation of a more efficacious set of G-quadruplexes stabilizers.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Citotoxinas
/
Proliferação de Células
/
Quadruplex G
/
Naftóis
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Molecules
Assunto da revista:
BIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália