STRUCTURE-ACTIVITY RELATIONSHIP STUDIES ON BENZOFURAN ANALOGS OF PROPAFENONE-TYPE MODULATORS OF TUMOR-CELL MULTIDRUG-RESISTANCE

A series of benzofurylethanolamine analogs of propafenone (1a) have be en prepared and evaluated for multidrug resistance-reversing activity in two in vitro assay systems. As for propafenones, an excellent corre lation of biological data with calculated lipophilicity values was fou nd for benzofurans, whereby the latter generally had lower activity/li pophilicity ratios. Almost identical slopes of the regression lines we re obtained for both propafenones and benzofurans. Multiple linear reg ression analysis of the complete data set yielded an equation with exc ellent predictive power (r(cross-valid)(2) = 0.968). Interaction measu rements with artificial membranes indicated that the differences in ac tivity between these two series of compounds are not due to difference s in the interaction pattern with biological membranes.