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Methylenebisphosphonates with Dienone Pharmacophore: Synthesis, Structure, Antitumor and Fluorescent Properties
Author(s) -
Makarov Mikhail V.,
Leonova Evgeniya S.,
Rybalkina Ekaterina Yu.,
Khrustalev Victor N.,
Shepel Nikolay E.,
Röschenthaler GerdVolker,
Timofeeva Tatiana V.,
Odinets Irina L.
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201100352
Subject(s) - pharmacophore , chemistry , stereochemistry , fluorescence , chemical synthesis , conjugate , combinatorial chemistry , in vitro , biochemistry , mathematical analysis , physics , mathematics , quantum mechanics
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.