Synthesis, brain antihypoxic activity and cell neuroprotection of 1-substituted-3,7-dimethylxanthines.
Five newly synthesised original compounds were investigated for acute toxicity, influence on hexobarbital sleeping time, effect on the locomotor activity, and brain antihypoxic activity. Two of the compounds were tested in a model of glutamate induced neurotoxicity in the brain cell culture using a cell viability test. Our studies indicate that compounds 2a-c and 4 prolonged the survival time of mice in the model of anoxic hypoxia. Only compound 3 expressed antihypoxic activity in the model of circulatory hypoxia, evaluated with a statistical significant increase of the survival time. Compound 4 (1-[3-(2,3-dihydro-3-oxobenzisosulfonazol2-yl)-propyl]-3,7-dimethylxanthine) in concentration range 0.3-3 microM statistically significantly antagonised the glutamate induced neurotoxicity. Compound 4 is important for further investigations on in vivo models of brain dementia.
Zlatkov
A
A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sofia, Bulgaria.
Peikov
P
P
Rodriguez-Alvarez
J
J
Danchev
N
N
Nikolova
I
I
Mitkov
J
J
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D017550:Spectroscopy, Fourier Transform Infrared; D014970:Xanthines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D018696:Neuroprotective Agents; D014970:Xanthines