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

Débora G. Salomón, Silvina M. Grioli, Maximiliano Buschiazzo, Evangelina Mascaró, Cristian Vitale, Gabriel Radivoy, Manuel Perez, Yagamare Fall, Enrique A. Mesri, Alejandro C. Curino, María M. Facchinetti

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19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)503-508
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume2
Issue number7
DOIs
StatePublished - Jul 14 2011

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Keywords

  • 1α,25-(OH) vitamin D
  • alkynylphosphonate analogues
  • cancer
  • cellular proliferation
  • hypercalcemia

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

Salomón, D. G., Grioli, S. M., Buschiazzo, M., Mascaró, E., Vitale, C., Radivoy, G., Perez, M., Fall, Y., Mesri, E. A., Curino, A. C., & Facchinetti, M. M. (2011). Novel alkynylphosphonate analogue of calcitriol with potent antiproliferative effects in cancer cells and lack of calcemic activity. ACS Medicinal Chemistry Letters, 2(7), 503-508. https://doi.org/10.1021/ml200034w