Chemical modification of Alisol B 23-acetate and their cytotoxic activity

Abstract

The twelve-protostane analogues were synthesized from alisol B 23-acetate and assessed for their in vitro antitumor activity against six different human and murine tumor cell lines. of the compounds synthesized, 23S-acetoxy-24R(25)- epoxy-11β,23S-dihydroxyprotost-13(17)-en-3-hy-droxyimine (12) exhibited significant cytotoxic activities against A549, SK-OV3, B16-F10, and HT1080 tumor cells with ED50 values of 10.0, 8.7, 5.2, and 3.1 μg/ml, respectively. Furthermore, 23S-acetoxy-13(17),24R(25)-diepoxy-11β- hydroxyprotost-3-one (5), 13(17),24R(25)-diepoxy-11β, 23S- dihydroxyprotostan-3-one (6), 24R,25-epoxy-11β,23S-dihydroxyprotost-13(17)- en-3-one (7), and 11β, 23S,24R,25-tetrahydroxyprotost-13(17)-en-3-one (9) showed moderate cytotoxic activities against B16-F10 and HT1080 tumor cells. These results mean that a hydroxyimino group at C-3 position in the protostane-type terpene enhances cytotoxic activity.