Synthesis and evaluation of anticancer activities of 2-or 4-substituted 3-(N-benzyltriazolylmethyl)-13α-oestrone derivatives

2- or 4-Substituted 3-N-benzyltriazolylmethyl-13 alpha-oestrone derivatives were synthesised via bromination of ring A and subsequent microwave-assisted, Pd-catalysed C(sp(2))-P couplings. The antiproliferative activities of the newly synthesised brominated and phosphonated compounds against a panel of human cancer cell lines (A2780, MCF-7, MDA-MB 231) were investigated by means of MTT assays. The most potent compound, the 3-N-benzyltriazolylmethyl-4-bromo-13 alpha-oestrone derivative exerted substantial selective cell growth-inhibitory activity against A2780 cell line with a submicromolar IC50 value. Computational calculations reveal strong interactions of the 4-bromo derivative with both colchicine and taxoid binding sites of tubulin. Disturbance of tubulin function has been confirmed by photometric polymerisation assay.

Automated summary

Newly synthesised brominated and phosphonated compounds were investigated for their antiproliferative activities against human cancer cell lines. One of the compounds showed substantial selective cell growth-inhibitory activity against the A2780 cell line and strong interactions with tubulin binding sites. The disturbance of tubulin function was confirmed by photometric polymerisation assay.