MOLECULAR BIOLOGY PROBLEMS OF DRUG DESIGN AND MECHANISM OF DRUG ACTION QUANTITATIVE INTERACTION BETWEEN THE STRUCTURES OF ORGANIC COMPOUNDS AND THEIR ABILITIES TO PENETRATE THE BLOOD-BRAIN BARRIER

Results of QSAR modeling of the interaction between the structures of organic compounds and their ability to penetrate the blood-brain barrier are presented. Published data for experimental values of logBB for humans (35 compounds) and rats (42 compounds) tested in vitro were used. We introduce descriptors calculated using the HYBOT program and present experimental coefficients of distribution for chemical compounds. The H-bond acceptor ability of molecules, which decreases permeability, is shown to have significant effects, as are the molecular polarizability and the total negative changes, which increase this ability for monofunctional chemical compounds. The successful treatment of a number of common central nervous system diseases (Alzheimer’s disease, stroke, brain tumors, etc.) requires rapid and easy access of drugs to the brain via the blood-brain barrier (BBB), and this is a difficult problem. The blood-brain barrier functions as a filter through which nutrients reach the brain via the bloodstream and metabolic products produced by nerve tissue move in the other direction. The BBB protects nerve tissue from microorganisms, toxins, and cellular and humoral immune system factors circulating in the blood. The BBB also prevents sub