Abstract
2,5-diketopiperazines are the simplest cyclic peptides found in nature, commonly biosynthesized from amino acids by different organisms, and represent a promising class of biologically active natural products. Their peculiar heterocyclic structure confers high stability against the proteolysis and constitutes a structural requirement for the active intestinal absorption. Furthermore, the diketopiperazine-based motif is considered as a novel brain shuttle for the delivery of drugs with limited ability to cross the blood-brain barrier (BBB) and can be proposed as an ideal candidate for the rational development of new therapeutic agents. Although these cyclic peptides have been known since the beginning of the 20th century, only recently have they attracted substantial interest with respect to the wide spectrum of their biological properties, including antitumor, antiviral, antifungal, antibacterial and antihyperglycemic activities. In addition to these, the most challenging function of the diketopiperazine derivatives is related with their remarkable neuroprotective and nootropic activity. The aim of the present paper is to provide an overview of the two major classes of diketopiperazines, the TRH-related and the unsaturated derivatives both characterized by a significant ability to protect against neurotoxicity in several experimental models. The neuroprotective profile of these compounds suggests that they may have a future utility in the therapy of neuronal degeneration in vivo, potentially through several different mechanisms.
Keywords: neurotoxicity, biosynthesized, pathogenesis, cytoprotective activity, 2-azetidinone, Alzheimer's disease, Amyotrophic lateral sclerosis, cyclic dipeptides, 2,5-diketopiperazine, neuroprotective peptides, Parkinson's disease, blood-brain barrier, antihyperglycemic
Mini-Reviews in Medicinal Chemistry
Title: 2,5-Diketopiperazines as Neuroprotective Agents
Volume: 12 Issue: 1
Author(s): C. Cornacchia, I. Cacciatore, L. Baldassarre, A. Mollica, F. Feliciani and F. Pinnen
Affiliation:
Keywords: neurotoxicity, biosynthesized, pathogenesis, cytoprotective activity, 2-azetidinone, Alzheimer's disease, Amyotrophic lateral sclerosis, cyclic dipeptides, 2,5-diketopiperazine, neuroprotective peptides, Parkinson's disease, blood-brain barrier, antihyperglycemic
Abstract: 2,5-diketopiperazines are the simplest cyclic peptides found in nature, commonly biosynthesized from amino acids by different organisms, and represent a promising class of biologically active natural products. Their peculiar heterocyclic structure confers high stability against the proteolysis and constitutes a structural requirement for the active intestinal absorption. Furthermore, the diketopiperazine-based motif is considered as a novel brain shuttle for the delivery of drugs with limited ability to cross the blood-brain barrier (BBB) and can be proposed as an ideal candidate for the rational development of new therapeutic agents. Although these cyclic peptides have been known since the beginning of the 20th century, only recently have they attracted substantial interest with respect to the wide spectrum of their biological properties, including antitumor, antiviral, antifungal, antibacterial and antihyperglycemic activities. In addition to these, the most challenging function of the diketopiperazine derivatives is related with their remarkable neuroprotective and nootropic activity. The aim of the present paper is to provide an overview of the two major classes of diketopiperazines, the TRH-related and the unsaturated derivatives both characterized by a significant ability to protect against neurotoxicity in several experimental models. The neuroprotective profile of these compounds suggests that they may have a future utility in the therapy of neuronal degeneration in vivo, potentially through several different mechanisms.
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Cornacchia C., Cacciatore I., Baldassarre L., Mollica A., Feliciani F. and Pinnen F., 2,5-Diketopiperazines as Neuroprotective Agents, Mini-Reviews in Medicinal Chemistry 2012; 12 (1) . https://dx.doi.org/10.2174/138955712798868959
DOI https://dx.doi.org/10.2174/138955712798868959 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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