GRAPHICAL ABSTRACT
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Abstract
Synthetic approaches for conjugating 3,5-bis(arylidene)-4-piperidones with bisphosphonate moiety were elaborated. These approaches are based either on reaction of Grignard reagent containing dioxolane protected 4-piperidone with tetraethyl ethylidenbisphosphonate followed by crotonic condensation with aromatic aldehydes or on Cu(i) catalyzed 1,3-cycloaddition of tetraethyl but-3-yne-1,1-diylbisphosphonate to N-(2-azidoethyl)-3,5-bis(arylidene)-4-piperidones resulting in corresponding 1,2,3-triazole derivatives. Cytotoxic activity of the synthesized conjugates was dependent on the length of linker connecting piperidone nitrogen atom and bisphosphonate residue. Triazole derivatives of 3,5-bis(arylidene)-4-piperidone series displayed moderate in vitro inhibitory properties towards HCT116 and MCF7 human cancer cell lines with IC50 values in the range of 5.0–7.5 μM, whereas conjugates with butylene linker between piperidone nitrogen atom and bisphosphonate moiety were significantly less active.