Novel alkynylphosphonate analogue of calcitriol with potent antiproliferative effects in cancer cells and lack of calcemic activity

SALOMÓN, D.G.; GRIOLI, S.; BUSCHIAZZO, M.; MASCARÓ, E.; VITALE, C.; RADIVOY, G.; PÉREZ, M.; FALL, Y.; MESRI, E.A.; CURINO, A.; FACCHINETTI, M.M.

ACS Medicinal Chemistry Letters

ACS

Año: 2011 vol. 2 p. 503 - 508

1948-5875

Here, we describe the design and synthesis of diethyl [(5Z,7E)-(1S,3R)-1,3-dihydroxy-9,10-secochola-5,7,10(19)-trien-23-in-24-yl] phosphonate (compound 10), which combines the low calcemic properties of phosphonates with the decreased metabolic inactivation due to the presence of a triple bond in C-24 and studied its in vitro effects on several cancer cell lines and its in vivo effects on blood calcium levels. We demonstrate that this compound is a potent antiproliferative vitamin D analogue, showing lack of calcemic effects in vivo