Synthesis of a novel analog of calcitriol and its biological evaluation as antitumor agent

FERRONATO, MARÍA JULIA; OBIOL, DIEGO JAVIER; ALONSO, ELIANA NOELIA; GUEVARA, JOSEFINA ALEJANDRA; GRIOLI, SILVINA MARIELA; MASCARÓ, MARILINA; RIVADULLA, MARCOS LOIS; MARTÍNEZ, ANDREA; GÓMEZ, GENEROSA; FALL, YAGAMARE; QUEVEDO, MARIO ALFREDO; CURINO, ALEJANDRO CARLOS; FACCHINETTI, MARÍA MARTA

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2019 vol. 185 p. 118 - 118

0960-0760

alcitriol analogs have shown promising potential as compounds to be used in cancer chemotherapy. This report presents the synthesis of a novel vitamin D 3 derivative with an amide and a carboxyl group in its side chain, called ML-344. In addition, we report its in vitro antitumor activity and its in vivo calcemic effects. We demonstrate that the analog decreases cell viability and retards cell migration of different breast, glioblastoma and head and neck cancer cell lines. Additionally, unlike calcitriol, ML-344 does not display citotoxicity to the murine non-malignant mammary cells and human astrocytes. In concordance with the antimigratory effects found in breast cancer cells, ML-344 decreased the invasive capacity and induced a rearrangement of the actin cytoskeleton in the LM3 breast cancer cell line. In relation to the in vivo studies, the analog did not cause hypercalcemic effects in CF1 mice administered daily at 5 μg/Kg of body weight during a period of 264 h. Finally, co