Molecules, Vol. 26, Pages 6124: A Novel Phenylpyrrolidine Derivative: Synthesis and Effect on Cognitive Functions in Rats with Experimental Ishemic Stroke

Molecules, Vol. 26, Pages 6124: A Novel Phenylpyrrolidine Derivative: Synthesis and Effect on Cognitive Functions in Rats with Experimental Ishemic Stroke Molecules doi: 10.3390/molecules26206124 Authors: Denis A. Borozdenko Aiarpi A. Ezdoglian Tatiana A. Shmigol Darya I. Gonchar Dmitri N. Lyakhmun Dmitri V. Tarasenko Yaroslav V. Golubev Elvira A. Cherkashova Daria D. Namestnikova Ilya L. Gubskiy Alexey A. Lagunin Leonid V. Gubsky Vladimir P. Chekhonin Sophia S. Borisevich Maxim A. Gureev Anastasia D. Shagina Nina M. Kiseleva Vadim V. Negrebetsky Yuri I. Baukov We performed an in silico, in vitro, and in vivo assessment of a potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (compound 1) as a potential prodrug for cognitive function improvement in ischemic brain injury. Using in silico methods, we predicted the pharmacological efficacy and possible safety in rat models. In addition, in silico data showed neuroprotective features of compound 1, which were further supported by in vitro experiments in a glutamate excitotoxicity-induced model in newborn rat cortical neuron cultures. Next, we checked whether compound 1 is capable of crossing the blood–brain barrier in intact and ischemic animals. Compound 1 improved animal behavior both in intact and ischemic rats and, even though the concentration in intact brains was low, we still observed a significant anxiety reduction and activity escalation. We used molecula...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research