The liposome partitioning system for correlating biological activities of imidazolidine derivatives

Abstract

The partitioning of 10 imidazolidines in various liposome/buffer systems (logK'm) has been determined and compared to partitioning in the n-octanol/buffer system (logP'). The logK'm, which was generally greater than the logP', increased or decreased upon the addition of dicetylphosphate (DCP) or stearylamine (STA), respectively, to dimyristoylphosphatidylcholine (DMPC) liposomes. Quantitative correlations of alpha 2-adrenergic potencies of imidazolidines have been made by regression analyses with logP', logK'm, binding affinity, and intrinsic activity. Both central and peripheral potencies correlated with logK'm but not with logP'. Multiple regressions yielded improved predictable quantification of these potencies. Thus, the liposomal membrane system shows certain advantages over the n-octanol/buffer system for the prediction of biological activities of the imidazolidines.