Pavlov S. Cerebroprotectiv activity (4-oxo- quinazoline -3-il)- alkyl (aryl) carboxolic acids in condition immobilization stress. (experimental research)

Dissertation is dedicated to experimental study of antioxidative and cerebro-protective activity of (4-oxo- quinazoline -3-il)- alkyl (aryl) carboxolic acids deriva-tives within immobilization stress simulation. As a consequence of pharmacological screening among 36 derivatives within in vitro and in vivo test, it has been singled out 5 compounds (ПК 53 (m-chloranilide 2-[4-oxo-3(4Н)- quinazoline] acetic acid); ПК 51 (m-trifluoride methyl anilide 2-[4-oxo-3(4Н)- quinazoline] acetic acid); ПК 37 (sulfanilamide 2-[4-oxo-3(4Н)- quinazoline] acetic acid); ПК 32 (n-ethoxocarboanilide 2-[6-nitro-4-oxo-3(4Н)- quinazoline] acetic acid); ПК 66 (4-[oxo-3(4Н)- quinazoline] benzoic acid), having high antioxidative and antiamnesic activity. "Structure-action" correlation analysis has shown, that antioxidative and antiamnesic activity of above mentioned compounds depends on substituent origine, its arrange-ment in aryl subsituent, as well as on their hydrophilia. It has been effected an advanced study of the most prospective ПК 66 com-pound in comparison with reference semax preparation within the model of chronic immobilization stress (HIS). Prescription of ПК 66 (10 mg/kg) within chronic immo-bilization stress test has resulted in increase of activity of catalase, superoxidedismu-tase, decrease of ion nitrite, APH and КPH, concentration 8-hydroxiguanine (8-OHG), increase of oxidation product ATP, decreased gene expressions of earlier reac-tion of c-fos, and decreased an amount of antiapoptic bcl-2- protein in CA1, in hippo-campus.