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

• Published in: Molecular pharmacology Vol. 27; no. 1; pp. 94 - 102
• Main Authors: BATRA, J. K, JURD, L, HAMEL, E
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.01.1985
• Subjects: Animals; Benzyl Compounds - pharmacology; Biological and medical sciences; Brain - metabolism; Colchicine - metabolism; Dioxoles - pharmacology; General pharmacology; Guanosine Triphosphate - metabolism; Kinetics; Leukemia L1210 - pathology; Macromolecular Substances; Medical sciences; Mice; Mitosis - drug effects; Mitotic Index - drug effects; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Structure-Activity Relationship; Tubulin - metabolism; Antineoplastic agent; Structure activity relation; Antitubulin
• ISSN: 0026-895X; 1521-0111

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.