The syntheses of C-13 epimeric 3-[(1-benzyl-1,2,3-triazol-4-yl)methoxy]-d-secoestrones
are reported. Triazoles were prepared from 3-(prop-2-inyloxy)-d-secoalcohols and p-substituted
benzyl azides via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The antiproliferative
activities of the products and their precursors were determined in vitro against a
panel of human adherent cervical (HeLa, SiHa and C33A), breast (MCF-7, MDA-MB-231,
MDA-MB-361 and T47D) and ovarian (A2780) cell lines by means of MTT assays. The orientation
of the angular methyl group and the substitution pattern of the benzyl group of the
azide greatly influenced the cell growth-inhibitory potential of the compounds. The
13beta derivatives generally proved to be more potent than their 13alpha counterparts.
Introduction of a benzyltriazolylmethyl group onto the 3-OH position seemed to be
advantageous. One 13alpha compound containing an unsubstituted benzyltriazolyl function
displayed outstanding antiproliferative activities against three cell lines.