Relationship between the hydrophobic physicochemical parameters and biological activity of some monoamine oxidase inhibitory drugs.
The MAO-B inhibitory effect of 11 propargylamine derivatives was determined in rat brain and rat liver and the concentration causing 50% inhibition (IC50) was calculated. The hydrophobic (lipophilicity, specific hydrophobic surface area) and hydrophilic (adsorption capacity on slightly acidic and alkaline surfaces, specific hydrophilic surface area on the same surfaces) physicochemical parameters of the MAO inhibitory drugs were determined by various adsorptive and reversed-phase chromatographic techniques. Stepwise regression analysis proved that only the hydrophilic parameters describing the interaction of drugs with alkaline surfaces exert a significant impact on the biological activity. These results make probably the direct interaction between the alkaline hydrophilic substructures of drugs and the secondary carboxyl groups of the target enzyme.
Forgács
E
E
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
Magyar
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012044:Regression Analysis; D013329:Structure-Activity Relationship; D013499:Surface Properties
D008996:Monoamine Oxidase Inhibitors