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 chemicals in a four-compartment system consisting of a catenary chain of alternating aqueous and lipoid phases is derived. Substitution of the transport rate parameters by their appropriate relations to the reference partition coefficient converts the kinetic equations into the quantitative structure-time-activity relationship (QSTAR) or its fixed-time equivalent, QSAR. The resulting expression describes satisfactorily the published data on antibacterial activity of n-alkyl amines as a function of their hydrophobicity. The hydrophobicity-activity profile consists of two or three smoothly connected linear parts. The model can be used in drug design, pharmacokinetics, and toxicology for description of the distribution of compounds in simple biosystems and in environmental sciences to predict the fate and effects of anthropogenic chemicals in ecological systems.