Structure-function studies with derivatives of 6-benzyl-1,3-benzodioxole, a new class of synthetic compounds which inhibit tubulin polymerization and mitosis.
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.
D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D003078:Colchicine / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D007939:Leukemia L1210 / Q000473:pathology; D046911:Macromolecular Substances; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D008940:Mitotic Index / Q000187:drug effects; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*
D001593:Benzyl Compounds; D004149:Dioxoles; D046911:Macromolecular Substances; D014404:Tubulin; D006160:Guanosine Triphosphate; D003078:Colchicine