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A Novel Phenylpyrrolidine Derivative: Synthesis and Effect on Cognitive Functions in Rats with Experimental Ishemic Stroke.

ABSTRACT: 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 molecular docking and molecular dynamics to support our hypothesis that compound 1 could affect the AMPA receptor function. In a rat model of acute focal cerebral ischemia, we studied the effects of compound 1 on the behavior and neurological deficit. An in vivo experiment demonstrated that compound 1 significantly reduced the neurological deficit and improved neurological symptom regression, exploratory behavior, and anxiety. Thus, here, for the first time, we show that compound 1 can be considered as an agent for restoring cognitive functions.

SUBMITTER: Borozdenko DA

PROVIDER: S-EPMC8541353 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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A Novel Phenylpyrrolidine Derivative: Synthesis and Effect on Cognitive Functions in Rats with Experimental Ishemic Stroke.

Borozdenko Denis A DA Ezdoglian Aiarpi A AA Shmigol Tatiana A TA Gonchar Darya I DI Lyakhmun Dmitri N DN Tarasenko Dmitri V DV Golubev Yaroslav V YV Cherkashova Elvira A EA Namestnikova Daria D DD Gubskiy Ilya L IL Lagunin Alexey A AA Gubsky Leonid V LV Chekhonin Vladimir P VP Borisevich Sophia S SS Gureev Maxim A MA Shagina Anastasia D AD Kiseleva Nina M NM Negrebetsky Vadim V VV Baukov Yuri I YI

Molecules (Basel, Switzerland) 20211011 20

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 <b>1</b>) 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 <b>1</b>, which were further supported by in vitro experiments in a glutamate excito ...[more]

PMID: 34684709

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Dataset Information

A Novel Phenylpyrrolidine Derivative: Synthesis and Effect on Cognitive Functions in Rats with Experimental Ishemic Stroke.

Publications

A Novel Phenylpyrrolidine Derivative: Synthesis and Effect on Cognitive Functions in Rats with Experimental Ishemic Stroke.

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