Proline-based topologic pyracetam analogs and their nootropic activity

Gudasheva, T. A.; Ostrovskaya, R. U.; Maksimova, F. V.; Chuppin, A. V.; Трофимов, С. С.; Lezina, V. P.; Воронина, Т. А.; Сколдинов, А. П.

doi:10.1007/bf00831694

Cited by 8 publications

(4 citation statements)

References 5 publications

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“…Doses of 0.1 and 1.0 mg/ kg were found to be effective (Table 1). In our previous experiments cyclo-(-Pro-Gly) improved memory also under conditions of undertraining [13]. It is important to stress that cyclo-(Pro-Gly) exerted neither stimulating nor depressant action on general psychomotor activity.…”

Section: Resultsmentioning

confidence: 77%

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Identification of a novel endogenous memory facilitating cyclic dipeptide cyclo‐prolylglycine in rat brain

Gudasheva¹,

Boiko²,

Akparov³

et al. 1996

FEBS Letters

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Using high-performance liquid chromatography, gaschromatography and chromato-mass spectrometry methods a novel endogenous cyclic dipeptide cyclo-prolylglycine was identified in rat brain. Its content according to gas chromatography is 2.8 + 0.3 nmol/g wet brain. Synthetic cyclo-prolylglycine has demonstrated antiamnesic activity in the passive avoidance test in rats at a dose of 0.1 mg/kg i.p. Cyclic dipeptide cyclo-prolylglycine seems to be a memory facilitating substance and its presence in rat brain suggests the existence of a new mechanism of memory regulation.Key words: Cyclo-prolylglycine; Endogenous cyclic dipeptide; Memory facilitating substance displays activity due to interaction with one vasopressin receptor subtype. We have found out, however, that unlike piracetam, which facilitates the initial processing of memory engram as well as consolidation, the dipeptide pGlu-Asn-NH2 improved only the phase of information input and retrieval, but did not influence consolidation [10]. On the other hand, proline-containing dipeptide analogues of piracetam facilitated consolidation [11]. The cyclic dipeptide cyclo-(Pro-Gly) turned out to be the most active of them [12]. This cyclic dipeptide can be assumed to be one of the endogenous ligands of hypothetic 'nootropic receptors', which selectively regulates the processes of training and memory. This work is devoted to the identification of endogenous cyclo-(Pro-Gly) in rat brain.

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Section: Resultsmentioning

confidence: 77%

“…213-214°C, [a]~ 2° 214°C in H20) was synthesized according to [13]. Pyrrolidino[1,2-a]-2,6-diazacycloheptanedione-l,5 (m.p.…”

Section: Chemicalsmentioning

confidence: 99%

Identification of a novel endogenous memory facilitating cyclic dipeptide cyclo‐prolylglycine in rat brain

Gudasheva¹,

Boiko²,

Akparov³

et al. 1996

FEBS Letters

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“…This regulation influences the interaction between IGF-1 signalling and MDM2-p53 pathways, resulting in a dose-dependent reduction in hfNSC cell death and apoptosis ( Figure 7 a) [ 67 ]. Importantly, cGP mimics the pharmacological effects of pramiracetam, including enhanced cognition [ 48 , 68 ], reduced anxiety [ 69 ], neuroprotection [ 51 ], analgesia [ 70 ], and antidepressant properties [ 71 ]. Mechanistic studies demonstrate that cGP modulates AMPA receptor-mediated currents in Purkinje neuronal cells [ 72 , 73 ].…”

Section: In Vitro and In Vivo Effectsmentioning

confidence: 99%

Exploring Sources, Biological Functions, and Potential Applications of the Ubiquitous Marine Cyclic Dipeptide: A Concise Review of Cyclic Glycine-Proline

Hu,

Lin,

Qin

et al. 2024

Marine Drugs

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Cyclic glycine-proline (cGP), a prevalent marine cyclic dipeptide, possesses a distinct pyrrolidine-2,5-dione scaffold, which contributes to the chemical diversity and broad bioactivities of cGP. The diverse sources from marine-related, endogenous biological, and synthetic pathways and the in vitro and in vivo activities of cGP are reviewed. The potential applications for cGP are also explored. In particular, the pivotal roles of cGP in regulating insulin-like growth factor-1 homeostasis, enhancing neuroprotective effects, and improving neurotrophic function in central nervous system diseases are described. The potential roles of this endogenous cyclic peptide in drug development and healthcare initiatives are also highlighted. This review underscores the significance of cGP as a fundamental building block in drug discovery with exceptional drug-like properties and safety. By elucidating the considerable value of cGP, this review aims to reignite interest in cGP-related research within marine medicinal chemistry and synthetic biology.

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“…We also used proline as pyrrolidine containing aminoacid for development of another peptide analogs of Piracetam [11, 12]. N -acyl moiety was added to proline residue to mimic carbonyl moiety that is present in pyroglutamic acid and is absent in proline Fig.…”

Section: Noopept a Dipeptide Nootropic Drugmentioning

confidence: 99%

Novel Technologies for Dipeptide Drugs Design and their Implantation

Gudasheva

Ostrovskaya

Середенин

2018

CPD

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The article is an overview of author’s data obtained in the framework of the project “The Creation of dipeptide preparations” at the V.V. Zakusov Institute of Pharmacology, Moscow, Russia. Advantages of dipeptides over longer peptides consist in that they are orally active owing to higher sta-bility and ability to penetrate biological barriers due to the presence of specific ATP–dependent trans-porters in enterocytes and blood-brain barrier. Two original approaches for dipeptide drugs design have been developed. Both of them are based on the idea of a leading role of central dipeptide fragment of the peptide chain beta-turn in the peptide-receptor interaction. The first approach, named “peptide drug-based design” represents the transformation of known nonpeptide drug into its dipeptide topological analog. The latter usually corresponds to a beta-turn of some regulatory peptide. The second approach represents the design of tripeptoide mimetic of the beta-turn of regulatory peptide or protein. The results of the studies, which led to the discovery of endogenous prototypes of the known non-peptide drugs piracetam and sulpiride, are presented herein. The paper discusses the process, based on the above-mentioned principles, that was used in designing of nontoxic, orally available, highly effective dipeptide drugs: nootropic noopept, dipeptide analog of piracetam; antipsychotic dilept, neurotensin tripeptoid analog; selective anxiolytic GB-115, tripeptoid analog of CCK-4, and potential neuroprotector GK-2, homodimeric dipeptide analog of NGF.

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Proline-based topologic pyracetam analogs and their nootropic activity

Cited by 8 publications

References 5 publications

Identification of a novel endogenous memory facilitating cyclic dipeptide cyclo‐prolylglycine in rat brain

Identification of a novel endogenous memory facilitating cyclic dipeptide cyclo‐prolylglycine in rat brain

Exploring Sources, Biological Functions, and Potential Applications of the Ubiquitous Marine Cyclic Dipeptide: A Concise Review of Cyclic Glycine-Proline

Novel Technologies for Dipeptide Drugs Design and their Implantation

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