KINETICS OF SUBCELLULAR-DISTRIBUTION OF COMPOUNDS IN SIMPLE BIOSYSTEMS AND ITS USE IN QSAR

An explicit expression describing the kinetics of distribution and, in some cases, biological activity in drugs and other anthropogenic chem icals in a four-compartment system consisting of a catenary chain of a lternating aqueous and lipoid phases is derived. Substitution of the t ransport rate parameters by their appropriate relations to the referen ce partition coefficient converts the kinetic equations into the quant itative structure-time-activity relationship (QSTAR) or its fixed-time equivalent, QSAR. The resulting expression describes satisfactorily t he published data on antibacterial activity of n-alkyl amines as a fun ction of their hydrophobicity. The hydrophobicity-activity profile con sists of two or three smoothly connected linear parts. The model can b e used in drug design, pharmacokinetics, and toxicology for descriptio n of the distribution of compounds in simple biosystems and in environ mental sciences to predict the fate and effects of anthropogenic chemi cals in ecological systems. (C) 1997 Academic Press Limited.