X-ray crystal structure of 10 beta-hydroxy-4 beta,5 beta P-epoxyestr-1-en-3,17-dione and antitumor activity of its congeners

Based on the biological properties of epoxyquinols from natural sources, th e title compound was synthesised as a potential antitumor agent. Its molecu lar structure was partially confirmed by NMR studies. The detailed structur e was established by X-ray analysis revealing two symmetry independent mole cules in the asymmetric unit each consisting of four fused rings with the C (10) beta-oriented hydroxy group and beta-oriented O atom bridging C(4) and C(5). The conformation of A ring in both conformers A and B is boat (B-3,B -6), while rings B and C are chairs (C-1(4)) and the five-membered D ring i s in an envelope (E-2) conformation. The in vitro antitumor activity of tit le compound and its 17 beta-acetoxy analogue against HeLa and Fem-x cells r evealed IC50 values of 5.7 and 7.1 mu M, and 2.25 and 1.58 mu M, respective ly. Corresponding quinols were tested on 47 cell lines with 10 beta-hydroxy -17 beta-acetoxyestra-1,4-dien-3-one being most active against leukemia SR cells (GI(50) = 0.17 mu M).