Structure-Activity Relationship Study of an Alkynylphosphonate and a Vynilphosphonate Analogues of Calcitriol

GRIOLI, SILVINA MARIELA; ALONSO, ELIANA NOELIA; MASCARÓ, EVANGELINA; STABILE, SANTIAGO ARMANDO; FERRONATO, MARÍA JULIA; QUEVEDO, MARIO ALFREDO; RADIVOY, GABRIEL; FACCHINETTI, MARÍA MARTA; VITALE, CRISTIAN ALEJANDRO; CURINO, ALEJANDRO CARLOS

MEDICINAL CHEMISTRY

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2021 vol. 16

1573-4064

ACKGROUND:1α,25-dihydroxyvitamin D3 (calcitriol) shows potent growth-inhibitory properties on different can-cer cell lines but its hypercalcemic effects have severely hampered its therapeutic application. Therefore, it is important todevelop synthetic calcitriol analogues that retain or even increase its antitumoral effects and lack hypercalcemic activity. Based on previous evidence of the potent antitumor effects of the synthetic alkynylphosphonate EM1 analogue, we have now synthesized a derivative called SG. OBJECTIVE:The aim of the present work is to evaluate the calcemic activity and the antitumor effect of SG, comparing these effects with those exerted by calcitriol and with those previously published for EM1. In addition, we propose to analyse by in silico studies the chemical structure-biological function relationship of these molecules. METHODS:We performed the synthesis of vinylphosphonate SG analogue; in vitro assays on different cancer cell lines; in vivo assays on mic