Abstract
AbstractAnalysis of uptake‐lipophilicity profiles of carbonylcyanide R‐phenylhydrazones (RC6H4NHNC(CN)2) in Paracoccus denitrificans and leukemic P‐388 cells showed that in early stages the drug distribution proceeds as simple diffusion in a multi‐phase system. After 10 min of partitioning only attainment of a lipophilic‐hydrophilic equilibrium was detected without observable chemical modification of the compounds. This fact allowed for straightforward formulation of two models for uncoupling of cellular oxidative phosphorylation, one based on protonophoric mechanism and the other involving covalent modification of energy transforming membrane proteins as the key step. Moreover, it enabled us to describe the dependence of uncoupling activity on lipophilicity using the uptake data and, thus, to reduce the number of adjustable parameters. The former (protonophoric) model exhibited a significantly better agreement with the experimental data in both biological systems.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call