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

SALOMÓN, DG; GRIOLI, S.M.; BUSCHIAZZO, M; MASCARÓ. E.; VITALE, CA; RADIVOY, G.E; PEREZ, M; FALL, Y.; MESRI, EA; CURINO, AC; FACCHINETTI, MM

ACS Medicinal Chemistry Letters

American Chemical Society

Lugar: Washington DC; Año: 2011 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.