Побудовано адекватні QSAR моделі «структура – показник проникнення речовин через
гематоенцефалічний бар’єр (ГЕБ) LogPS» для органічних сполук різних класів. Проведено структурну та фізико-хімічну інтерпретацію моделей. Виявлено, що проникнення
речовин через ГЕБ в значній мірі обумовлено гідрофобним чинником (30%). Визначено
деякі фрагменти молекул, що сприяють або перешкоджають проникненню речовин через ГЕБ.
The aim of this work is to analyze the influence of the structure of organic compounds on their
ability to penetrate the blood-brain barrier (BBB) using the values of LogPS (logarithm of the
product of permeability and surface area of metabolism, which is a measure of the transfer of
compounds from the blood to the brain and reflects the degree of penetration of the substance
into the brain without relative binding to proteins). The study of the permeability of BBB is
necessary both for the development of new drugs for which the CNS is a biointerference, and
for the development of effective ways of treating diseases of the brain. At the initial stage of the study, the object of this work was the database of 89 organic
compounds with a known value LogPS. Subsequently, the database was expanded to 177
compounds by additional data retrieval from various scientific sources. For all investigated
compounds the structural parameters were calculated using the SiRMS method, which is
based on the simplex representation of the molecular structure. QSAR models were developed
using the “Partial Least Squares method” (PLS) and Random Forest (RF).
The adequate «structure – LogPS» 2D-QSAR models were obtained for organic compounds of
different classes. Physico-chemical and structural interpretation of the of the obtained QSAR
models was carried out. Among various physical and chemical factors, the hydrophobic factors
have the greatest influence on BBB permeability (30%). The study proved that polar groups
and donor/acceptor of H-bond (–COOH, -NH2, -OH, -S(O)2-, -CO-, -NH-CO-) negatively
affect the penetration ability of compounds through BBB. Contrary, aromatic fragments,
halogens (–F, -Cl) and such fragments as different alkyls and -N(C2H5)2 have a positive effect
on the penetration. The developed QSAR models were included in the expert system to predict
the penetration of substances through the BBB.
