Synthesis of Bleomycin-Inspired RNA Ligands Targeting the Biogenesis of Oncogenic miRNAs.
J Med Chem
; 66(15): 10639-10657, 2023 08 10.
Article
em En
| MEDLINE
| ID: mdl-37449818
ABSTRACT
Noncoding RNAs (ncRNAs) play pivotal roles in the regulation of gene expression and represent a promising target for the development of new therapeutic approaches. Among these ncRNAs, microRNAs (miRNAs or miRs) are involved in the regulation of gene expression, and their dysregulation has been linked to several diseases such as cancers. Indeed, oncogenic miRNAs are overexpressed in cancer cells, thus promoting tumorigenesis and maintenance of cancer stem cells that are resistant to chemotherapy and often responsible for therapeutic failure. Here, we describe the design and synthesis of new small-molecule RNA binders able to inhibit the biogenesis of oncogenic miRNAs and target efficiently cancer stem cells. Through the biochemical study of their interaction with the target and thanks to intracellular assays, we describe the structure-activity relationships for this new series of RNA ligands, and we identify compounds bearing a very promising antiproliferative activity against cancer stem cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
França