Methylenebisphosphonates with dienone pharmacophore: synthesis, structure, antitumor and fluorescent properties.
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.
A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, Russian Federation.
Mikhail V
MV
Makarov
Evgeniya S
ES
Leonova
Ekaterina Yu
EY
Rybalkina
Victor N
VN
Khrustalev
Nikolay E
NE
Shepel
Gerd-Volker
GV
Röschenthaler
Tatiana V
TV
Timofeeva
Irina L
IL
Odinets
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005453:Fluorescence; D006801:Humans
D000970:Antineoplastic Agents; D004164:Diphosphonates