Synthesis and evaluation of cytotoxic and Na/K-ATP-ase inhibitory activity of selected 5α-oleandrigenin derivatives.

Oleandrin, the major biologically active constituent of shrub Nerium oleander preparations of which have been used in traditional Mediterranean and Asian medicine, attracts a great deal of attention due to its pronounced anticancer activity. The synthesis of oleandrigenin model, 16β-hydroxy-3β-methoxy-5α-card-20(22)-enolide 16-acetate, from androstenolone acetate through 17β-(3-furyl)-intermediates has been developed. Several related 17β-(butenolidyl)- and 17β-(furyl)-androstane derivatives were synthesized and tested for in vitro cytotoxic and Na/K-ATP-ase inhibitory activities. Comparison of Na/K-ATP-ase inhibitory and cytotoxic activity underlines complex nature of the relationship.