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

  • ACS Med Chem Lett. 2011 Apr 11;2(7):503-8. doi: 10.1021/ml200034w.
Débora G Salomón  1 ,  Silvina M Grioli  1 ,  Maximiliano Buschiazzo  1 ,  Evangelina Mascaró  2 ,  Cristian Vitale  2 ,  Gabriel Radivoy  2 ,  Manuel Perez  3 ,  Yagamare Fall  3 ,  Enrique A Mesri  4 ,  Alejandro C Curino  1 ,  María M Facchinetti  1
Affiliations
  • 1. Laboratorio de Biología Básica del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca (INIBIBB), 8000 , Bahía Blanca, Argentina.
  • 2. Departamento de Química, Instituto de Química del Sur (Inquisur-Conicet), Universidad Nacional del Sur , 8000 Bahía Blanca, Argentina.
  • 3. Departamento de Química Orgánica, Facultad de Química, Universidad de Vigo, 36200 , España.
  • 4. Microbiology and Immunology & Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, Florida, 33136, United States.
PMID: 24900339 DOI: 10.1021/ml200034w
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.

Keywords
1α,25-(OH)2 vitamin D3; alkynylphosphonate analogues; cancer; cellular proliferation; hypercalcemia.