Structure-function studies with derivatives of 6-benzyl-1,3- benzodioxole, a new class of synthetic compounds which inhibit tubulin polymerization and mitosis

JK Batra, L Jurd and E Hamel

A new class of synthetic antineoplastic compounds, derivatives of 6- benzyl-1,3-benzodioxole, has significant antimitotic activity. These compounds inhibit microtubule assembly and are competitive inhibitors of the binding of colchicine to tubulin. Both their structure and their partial inhibition of tubulin-dependent GTP hydrolysis indicate that they are most comparable to podophyllotoxin of all known antimitotic drugs. Maximum activity required an intact dioxole ring, a methoxy or ethoxy substituent at position 5, and, on the benzyl moiety at position 6, a para-methoxy group. Additional methoxy groups on the benzyl substituent, to increase the apparent structural similarity to podophyllotoxin, resulted in major reduction of the antitubulin activity of these drugs.

Volume 27, Issue 1, pp. 94-102, 01/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics