Novel calcitriol analogue with an oxolane group: In vitro, in vivo, and in silico studies

OBIOL, DIEGO J.; MARTÍNEZ, ANDREA; FERRONATO, MARÍA J.; QUEVEDO, MARIO A.; GRIOLI, SILVINA M.; ALONSO, ELIANA N.; GÓMEZ, GENEROSA; FALL, YAGAMARE; FACCHINETTI, MARÍA M.; CURINO, ALEJANDRO C.

ARCHIV DER PHARMAZIE.

WILEY-V C H VERLAG GMBH

Año: 2019 vol. 352

0365-6233

he active form of vitamin D 3 , calcitriol, is a potent antiproliferative compound. However, when effective antitumor doses of calcitriol are used, hypercalcemic effects are observed, thus blocking its therapeutic application. To overcome this problem, structural analogues have been designed with the aim of retaining or even increasing the antitumor effects while decreasing its calcemic activity. This report aims at gaining insights into the structure?activity relationships of the novel oxolane-containing analogue, AM-27, recently synthesized. We herein demonstrate that this compound has antiproliferative and antimigratory effects in squamous cell carcinoma, glioblastoma, and breast cancer cell lines. Analyses of the mechanisms underlying the AM-27 effects on cell viability revealed induction of apoptosis by the analogue. Importantly, nonmalignant cell lines were little or not affected by the compound. In addition, the analogue did not produce hypercalcemia in mice. Also, in silico st