ANTITUMOR 2,3-DIHYDRO-2-(ARYL)-4(1H)-QUINAZOLINONE DERIVATIVES - INTERACTIONS WITH TUBULIN

A series of derivatives of 2,3-dihydro-2-(aryl)-4(1H)-quinazolinone (D HQZ) with known anti-tumor activity was re-evaluated in the National C ancer Institute cancer cell line screen. Analysis by the COMPARE algor ithm suggested that their cytotoxicity derived from interactions with tubulin. Significant inhibition of tubulin assembly and of the binding of radiolabeled colchicine to tubulin was demonstrated with several o f the compounds, particularly NSC 145669, 175635, and 175636. The DHQZ derivatives are structurally analogous to a number of antimitotic age nts, flavonols and derivatives of 2-styrylquinazolin-4(3H)-one and of 2-phenyl-4-quinolone. Structure-activity analogies between these agent s, the combretastatins, and the colchicinoids were analyzed and summar ized.