Steganacin

Abstract: A new series of 23 synthetic analogues of the naturally occurring antitumor lignan steganacin was tested for the inhibition of microtubule assembly in vitro. Interestingly, (+/-)-isopicrostegane (I50 = 5 microM) was found to be almost as active as (+/-)-steganacin(I50 = 3.5 microM). On the other hand, racemic isodeoxypodophyllotoxin has an inhibiting activity of microtubule assembly comparable to that of (-)-podophyllotoxin, whereas (-)-isodeoxypodophyllotoxin is totally inactive.

Abstract: Summary Steganacin, a newly isolated tumor inhibitor, completely inhibits cleavage in sea urchin eggs at 3 × 10−7m by preventing the formation of the mitotic apparatus. Steganacin inhibits the polymerization of tubulin in vitro and also causes a slow depolymerization of preformed microtubules. Optical ultracentrifuge studies of steganacin-treated tubulin show a small reduction in 20 S and 30 S peaks at 0°. In electron microscope studies the ring structure of tubulin is seen at 0° but disappears if the temperature of tubulin incubated with steganacin is raised to 37°. Steganacin inhibits the binding of colchicine to tubulin and thus resembles podophyllotoxin, which also competitively inhibits colchicine binding. Steganacin has a trimethoxybenzene ring and probably interacts with that portion of the colchicinebinding site that recognizes the trimethoxybenzene ring of colchicine.