2. Academic Validation
  3. Novel alkynylphosphonate analogue of calcitriol with potent antiproliferative effects in cancer cells and lack of calcemic activity

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

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.

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