title: Novel alkynylphosphonate analogue of calcitriol with potent antiproliferative effects in cancer cells and lack of calcemic activity.
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.
authors.affiliation: Laboratorio de Biología Básica del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca (INIBIBB), 8000 , Bahía Blanca, Argentina.
authors.forename: Débora G
authors.initials: DG
authors.lastname: Salomón
authors.affiliation: Laboratorio de Biología Básica del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca (INIBIBB), 8000 , Bahía Blanca, Argentina.
authors.forename: Silvina M
authors.initials: SM
authors.lastname: Grioli
authors.affiliation: Laboratorio de Biología Básica del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca (INIBIBB), 8000 , Bahía Blanca, Argentina.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Buschiazzo
authors.affiliation: Departamento de Química, Instituto de Química del Sur (Inquisur-Conicet), Universidad Nacional del Sur , 8000 Bahía Blanca, Argentina.
authors.forename: Evangelina
authors.initials: E
authors.lastname: Mascaró
authors.affiliation: Departamento de Química, Instituto de Química del Sur (Inquisur-Conicet), Universidad Nacional del Sur , 8000 Bahía Blanca, Argentina.
authors.forename: Cristian
authors.initials: C
authors.lastname: Vitale
authors.affiliation: Departamento de Química, Instituto de Química del Sur (Inquisur-Conicet), Universidad Nacional del Sur , 8000 Bahía Blanca, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Radivoy
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Vigo, 36200 , España.
authors.forename: Manuel
authors.initials: M
authors.lastname: Perez
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Vigo, 36200 , España.
authors.forename: Yagamare
authors.initials: Y
authors.lastname: Fall
authors.affiliation: Microbiology and Immunology & Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine , Miami, Florida, 33136, United States.
authors.forename: Enrique A
authors.initials: EA
authors.lastname: Mesri
authors.affiliation: Laboratorio de Biología Básica del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca (INIBIBB), 8000 , Bahía Blanca, Argentina.
authors.forename: Alejandro C
authors.initials: AC
authors.lastname: Curino
authors.affiliation: Laboratorio de Biología Básica del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca (INIBIBB), 8000 , Bahía Blanca, Argentina.
authors.forename: María M
authors.initials: MM
authors.lastname: Facchinetti
keywords: 1α,25-(OH)2 vitamin D3; alkynylphosphonate analogues; cancer; cellular proliferation; hypercalcemia