Chromene Derivatives as Selective TERRA G-Quadruplex RNA Binders with Antiproliferative Properties.
G-quadruplex DNA
TERRA
biological assays
circular dichroism
docking
mass spectrometry
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
28 Apr 2022
28 Apr 2022
Historique:
received:
18
01
2022
revised:
20
04
2022
accepted:
22
04
2022
entrez:
28
5
2022
pubmed:
29
5
2022
medline:
29
5
2022
Statut:
epublish
Résumé
In mammalian cells, telomerase transcribes telomeres in large G-rich non-coding RNA, known as telomeric repeat-containing RNA (TERRA), which folds into noncanonical nucleic acid secondary structures called G-quadruplexes (G4s). Since TERRA G4 has been shown to be involved in telomere length and translation regulation, it could provide valuable insight into fundamental biological processes, such as cancer growth, and TERRA G4 binders could represent an innovative strategy for cancer treatment. In this work, the three best candidates identified in our previous virtual screening campaign on bimolecular DNA/RNA G4s were investigated on the monomolecular Tel DNA and TERRA G4s by means of molecular modelling simulations and in vitro and in cell analysis. The results obtained in this work highlighted the stabilizing power of all the three candidates on TERRA G4. In particular, the two compounds characterized by a chromene scaffold were selective TERRA G4 binders, while the compound with a naphthyridine core acted as a dual Tel/TERRA G4-binder. A biophysical investigation by circular dichroism confirmed the relative stabilization efficiency of the compounds towards TERRA and Tel G4s. The TERRA G4 stabilizing
Identifiants
pubmed: 35631373
pii: ph15050548
doi: 10.3390/ph15050548
pmc: PMC9147070
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Italian Association for Cancer Research
ID : 21588
Organisme : Italian Association for Cancer Research
ID : 21850
Organisme : PRIN 2017
ID : 201744BN5T
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