Synthesis and biological evaluation of new 6-s-cis locked 1,2,25-trihydroxyprevitamin D3 analogues

An efficient synthesis of several diastereomers of 2-hydroxy substituted 1α,25-dihydroxyprevitamin D3 derivatives was accomplished utilizing a practical route to the A-ring synthon. The biological activity of the analogues was evaluated in vitro. All the synthesized derivatives demonstrated low affinity for the vitamin D receptor and vitamin D-binding protein compared with 1α,25-dihydroxyvitamin D3, the natural hormone. 1α,2β,25-trihydroxy-19-nor-pre-D3 was the most potent of the analogues in inhibiting proliferation of MCF-7 cells but requires higher EC50 concentrations than 1α,25-dihydroxyvitamin D3.

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