| Summary: | The combination of an androstane-3,17-diol nucleus and a 2β-<i>N</i>-alkylamidopiperazino sidechain is important for the anticancer activity of a new family of steroid derivatives. As the structure-activity relationship studies have so far been limited to the beta orientation of the substituent at position 2 of the steroid nucleus, a series of analogs (compounds <b>1</b>–<b>4</b>) were synthesized to investigate the impact on biological activity of A-ring substitution. Nuclear magnetic resonance (NMR) analysis, especially using a series of 2D experiments, such as correlation spectroscopy (COSY), homonuclear Overhauser effect spectroscopy (NOESY), heteronuclear single-quantum correlation (HSQC), and heteronuclear multiple-bond correlation (HMBC) provided crucial information that was found essential in confirming the sidechain position and orientation of compounds <b>1</b>–<b>4</b>. Assessment of their antiproliferative activity on leukemia HL-60 cells confirmed the best efficiency of the 2β-sidechain/3α-OH orientation (compound <b>1</b>) compared to the other configurations tested (compounds <b>2</b>–<b>4</b>).
|
|---|