Methylenebisphosphonates with dienone pharmacophore: synthesis, structure, antitumor and fluorescent properties.
Arch Pharm (Weinheim)
; 345(5): 349-59, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22213431
ABSTRACT
The synthesis and the antitumor activity and fluorescent properties screening of novel bisphosphonate conjugates with cytotoxic 3,5-bis((hetero)arylidene)-4-piperidone residues were performed. The facile and rapid synthetic route was based on the aza-Michael addition of NH-3,5-bis((hetero)arylidene)-4-piperidones to tetraethyl ethylidenebisphosphonate. The synthesized compounds displayed high inhibitory properties towards Caov3, A549, PC3, and KB 3-1 human carcinoma cell lines. Among those, compounds bearing 4-cyano-phenyl and 3-pyridinyl substituents were revealed as the most active drug candidates with IC(50) values in the range of 0.5-2.5 µM. Methylenebisphosphonate with 4-Me(2) N-C(6) H(4) groups in the piperidone framework possessing fluorescence properties may be of interest for visualization of BPs skeletal distribution and cellular uptake in bones and other tissues.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Difosfonatos
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Arch Pharm (Weinheim)
Ano de publicação:
2012
Tipo de documento:
Article