Actoprotective activity of 6-monosubstituted 3-R-6,7-dihydro-2H-[1,2,4]triazino-[2,3-c]quinazoline-2-ones

Abstract

Aim. Currently drugs with actoprotective activity are increasingly applied in sport medicine, military medicine, space medicine, emergence medicine, deep-see medicine rehabilitative medicine during high physical stresses. Purposeful search of actoprotectors is quite urgent considering the fact that mentioned drug type insignificantly present on pharmaceutical market and have numerous side-effects. Considering the mentioned above facts we were aimed to conduct the purposeful search of compounds with actoprotective action among previously unknown condensed quinazoline derivatives, as well as estimate «structure-actoprotective activity» relationships among studied compounds. Material and methods. Aimed to the search of novel compounds with actoprotective activity we studied prospective and previously unknown 6-monosubstituted 3-R-6,7-dihydro-2H-[1,2,4]triazino-[2,3-c]quinazoline-2-ones using «swimming test» at temperature 24-26 Co with additional loads (10% of experimental animal body weight). Experiments were conducted on «Wistar» white rats. «Mildronat» was used as reference-drug. Obtained data allowed to detect the prospective compounds that were used for detailed studies. Results and discussion. It was found, that most of studied compounds increased the swimming duration of experimental animals at normal temperature while intragastric administration in 50 mg/kg dose. It was estimated, that compounds 1.1, 1.3, 2.3, 3.4 and 4.3 reveal the higher actoprotective activity comparing to reference drug «Mildronate». The analysis of «structure-biological activity» relationships showed that actoprotective activity of studied drugs is caused by the presence of hydrogenated [1,2,4]triazino[2,3-c]quinazoline cycle as well as by 2(4)-flourophenyl substituent of 6th position. The reliable relationships between actoprotective, antiradical activity and lipophility among 6-monosubstituted 3-R-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones on the results of studies were not revealed. «Structure-actoprotective activities» relationships data, that were obtained, allowed to create the strategy of purposeful search of compounds with actoprotective activity among [1,2,4]triazino[2,3-c]quinazolines substituted. Conclusion. The actoprotective activity of novel 6-monosubstituted 3-R-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones was detected. The reliable relationships between actoprotective, antiradical activity and lipophility among 6-monosubstituted 3-R-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones on the results of studies were not revealed.

Keywords

• 6-monosubstituted 3-R-6 7-dihydro-2H-[1 2 4]triazino[2 3-c]quinazoline-2-ones
• Physical Endurance
• Actoprotective and Antiradicale Activity