Synthesis, Brain Antihypoxic Activity and cell Neuroprotection of Ester Derivatives of 7-Theophylline acetic acid
By Alexander B. Zlatkov, Plamen T. Peikov, Jose Rodriguez-Alvarez, Irina Nikolova , Nikolai D. Danchev
The synthesis of three ester derivatives of 7-theophylline-acetic acid and hydroxyl group containing compounds was studied by DCC/4-DMAP – mediated esterification under mild conditions. The structures of synthesized compounds were proved by microanalyses, UV-, IR- and 1H-NMR data. Acute toxicity assessment of the compounds in mice shows less toxicity than standard theophylline. Compounds 3a-c posses depressive activity on CNS (increasing of pentobarbital sleeping time and decreasing of spontaneous locomotor activity). In in vivo experiments of brain anoxic hypoxia, compounds 3a and 3c in a dose 1/10 of LD50, result in increase of the mean survival time of mice. These results indicate that compounds 3a and 3c are very prospective for further pharmacological and biochemical experiments in relation to the treatment of brain neurodegenerative disorders.
Keywords : 7-theophylline acetic acid, esters, acute toxicity, brain antihypoxic activity.