Ferrocene modified analogues of imatinib and nilotinib as potent anti-cancer agents.
Journal
RSC medicinal chemistry
ISSN: 2632-8682
Titre abrégé: RSC Med Chem
Pays: England
ID NLM: 101759460
Informations de publication
Date de publication:
25 May 2023
25 May 2023
Historique:
received:
20
01
2023
accepted:
13
03
2023
pmc-release:
14
03
2024
medline:
30
5
2023
pubmed:
30
5
2023
entrez:
30
5
2023
Statut:
epublish
Résumé
The unique features of ferrocene and the need for development of targeted anticancer drugs inspired the design, synthesis and biological evaluation of ferrocenyl modified tyrosine kinase inhibitors by replacing the pyridyl moiety in imatinib and nilotinib generalized structures with a ferrocenyl group. A series of seven new ferrocene analogues were synthesized and evaluated for their anticancer activity in a panel of bcr-abl positive human malignant cell lines using imatinib as a reference drug. The metallocenes exhibited a dose-dependent inhibition on malignant cell growth with varying antileukemic activity. The most potent analogues were compounds 9 and 15a showing comparable or even superior efficacy to the reference. Their cancer selectivity indices suggest a favorable selectivity profile, indicating a 250 times higher preferential activity of 15a towards malignantly transformed K-562 cells and an even twice greater one (500) of 9 in the LAMA-84 leukemic model as compared to the normal murine fibroblast cell line.
Identifiants
pubmed: 37252096
doi: 10.1039/d3md00030c
pii: d3md00030c
pmc: PMC10211329
doi:
Types de publication
Journal Article
Langues
eng
Pagination
880-889Informations de copyright
This journal is © The Royal Society of Chemistry.
Déclaration de conflit d'intérêts
There are no conflicts to declare.
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