Effect on AMPA receptors and lipophilicity of substituted pyridoindoles as potential neuroprotectors

Abstract

The effect of the chemical nature of substituents (–H, –CH3–, –OCH3, –F and –Cl) introduced into the tricyclic fragment of hydrogenated pyrido[4,3-b]indoles on the compounds ability to positively modulate the activity of ionotropic glutamate AMPA receptors have been studied. The unsubstituted derivative, compounds with a methyl group and a fluorine atom were found to have the highest bioactivity in this test. The partition coefficients of the synthesized derivatives in the system 1-octanol/buffer pH 7.4 in the temperature range of 293.15–313.15 K have been measured. It has been found that as the lipophilicity of the compounds studied increases, the maximum biological activity is achieved at a higher concentration of the administered substance. The thermodynamic transfer functions of the studied substances from aqueous medium to organic phase have been calculated.