Therapeutic Effect of Novel Cyanopyrrolidine-Based Prolyl Oligopeptidase Inhibitors in Rat Models of Amnesia; Frontiers in Chemistry; Vol. 9

Therapeutic Effect of Novel Cyanopyrrolidine-Based Prolyl Oligopeptidase Inhibitors in Rat Models of Amnesia; Frontiers in Chemistry; Vol. 9

Podrobná bibliografie
Parent link:Frontiers in Chemistry
Vol. 9.— 2021.— [780958, 15 p.]
Korporativní autor: Национальный исследовательский Томский политехнический университет Инженерная школа новых производственных технологий Научно-образовательный центр Н. М. Кижнера
Další autoři: Zolotov N. N. Nikolay Nikolaevich, Shchepyotkin I. A. Igor Aleksandrovich, Voronina T. A. Tatjyana Aleksandrovna, Pozdnev V. F. Vladimir Fedorovich, Khlebnikov A. I. Andrey Ivanovich, Krylova I. V. Irina Viktorovna, Quinn M. T. Mark
Shrnutí:Title screen
Prolyl oligopeptidase (POP) is a large cytosolic serine peptidase that is altered in patients with Alzheimer's disease, Parkinsonian syndrome, muscular dystrophies, and other denervating diseases. Thus, POP may represent a relevant therapeutic target for treatment of neuropsychiatric disorders and neurodegenerative diseases. Here, we report the characterization of five novel cyanopyrrolidine-based compounds (BocTrpPrdN, BocGlyPrdN, CbzMetPrdN, CbzGlnPrdN, and CbzAlaPrdN) and show that they are potent inhibitors of POP and are predicted to penetrate the blood-brain barrier (BBB). Indeed, we show that CbzMetPrdN penetrates the rat BBB and effectively inhibits POP in the brain when administered intraperitoneally. Furthermore, molecular modeling confirmed these compounds likely inhibit POP via interaction with the POP catalytic site. We evaluated protective effects of the cyanopyrrolidine-based POP inhibitors using scopolamine- and maximal electroshock-induced models of amnesia in rats and showed that BocTrpPrdN, BocGlyPrdN, CbzMetPrdN, and CbzGlnPrdN significantly prolonged conditioned passive avoidance reflex (CPAR) retention time when administered intraperitoneally (1 and 2 mg/kg) before evaluation in both models of amnesia, although CbzAlaPrdN was not effective in scopolamine-induced amnesia. Our data support previous reports on the antiamnesic effects of prolinal-based POP inhibitors and indicate an important role of POP in the regulation of learning and memory processes in the CNS.
Jazyk:angličtina
Vydáno: 2021
Témata:
электронный ресурс
труды учёных ТПУ
Alzheheimers disease
prolyl oligopeptdases
brain
blood brain barrier
cyanopyrrolidine derivatives
antiamnesic activity
conditioned passive avoidance reflex
болезнь Альцгеймера
головной мозг
терапевтическое действие
ингибиторы
амнезия
On-line přístup:https://doi.org/10.3389/fchem.2021.780958
Médium: Elektronický zdroj Kapitola
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=667438

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