Methylenebisphosphonates with Dienone Pharmacophore: Synthesis, Structure, Antitumor and Fluorescent Properties

作者：Makarov Mikhail V; Leonova Evgeniya S; Rybalkina Ekaterina Yu; Khrustalev Victor N; Shepel Nikolay E; Roeschenthaler Gerd Volker; Timofeeva Tatiana V; Odinets Irina L^*

来源：Archiv der Pharmazie, 2012, 345(5): 349-359.

DOI：10.1002/ardp.201100352

• 3
• 5-Bis((hetero)arylidene)-4-piperidones
• Antitumor activity
• Fluorescence labeling
• Methylenebisphosphonates
• Synthesis

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 IC50 values in the range of 0.52.5?mu M. Methylenebisphosphonate with 4-Me2N-C6H4 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.

• 出版日期2012-5