Recent advances in the study of (–)clausenamide: chemistry, biological activities and mechanism of action
Clausenamide (clau) is one of seven novel compounds isolated from Clausena lansium (Lour) skeels. Clau is unusual in that it contains 4 chiral centers yielding 8 pairs of enantiomers. After identification of the configuration of these enantiomers, the synthesis of 16 enantiomers, including optically...
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Elsevier
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629111/ |
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pubmed-46291112015-11-17 Recent advances in the study of (–)clausenamide: chemistry, biological activities and mechanism of action Chu, Shi-feng Zhang, Jun-tian Review Clausenamide (clau) is one of seven novel compounds isolated from Clausena lansium (Lour) skeels. Clau is unusual in that it contains 4 chiral centers yielding 8 pairs of enantiomers. After identification of the configuration of these enantiomers, the synthesis of 16 enantiomers, including optically active clau and (+) and (–)clau was carried out. During this study, many stereochemical and synthetic difficulties were solved and the Baldwin principle was updated. Production scale is now sufficient to meet the needs of clinical practice. In a pharmacological study numerous models and indicators showed that (–)clau is the active enantiomer, while (+)clau is inactive and elicits greater toxicity than (–)clau. The principal pharmacological effects of (–)clau are to increase cognition, demonstrated in ten models of memory impairment, as well as to inhibit β-amyloid (Aβ) toxicity, blocking neurofibrillary tangle formation by inhibiting the phosphorylation of tau protein. This anti-dementia effect is characterized by increased synaptic plasticity both in efficacy and in structure and provides new support for the theory that synaptic loss is the main cause of dementia. (–)Clau is considered to be a promising drug candidate for treatment of Alzheimer׳s disease and other neurodegenerative disorders. Elsevier 2014-12 2014-11-20 /pmc/articles/PMC4629111/ /pubmed/26579412 http://dx.doi.org/10.1016/j.apsb.2014.10.004 Text en © 2014 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Chu, Shi-feng Zhang, Jun-tian |
| spellingShingle |
Chu, Shi-feng Zhang, Jun-tian Recent advances in the study of (–)clausenamide: chemistry, biological activities and mechanism of action |
| author_facet |
Chu, Shi-feng Zhang, Jun-tian |
| author_sort |
Chu, Shi-feng |
| title |
Recent advances in the study of (–)clausenamide: chemistry, biological activities and mechanism of action |
| title_short |
Recent advances in the study of (–)clausenamide: chemistry, biological activities and mechanism of action |
| title_full |
Recent advances in the study of (–)clausenamide: chemistry, biological activities and mechanism of action |
| title_fullStr |
Recent advances in the study of (–)clausenamide: chemistry, biological activities and mechanism of action |
| title_full_unstemmed |
Recent advances in the study of (–)clausenamide: chemistry, biological activities and mechanism of action |
| title_sort |
recent advances in the study of (–)clausenamide: chemistry, biological activities and mechanism of action |
| description |
Clausenamide (clau) is one of seven novel compounds isolated from Clausena lansium (Lour) skeels. Clau is unusual in that it contains 4 chiral centers yielding 8 pairs of enantiomers. After identification of the configuration of these enantiomers, the synthesis of 16 enantiomers, including optically active clau and (+) and (–)clau was carried out. During this study, many stereochemical and synthetic difficulties were solved and the Baldwin principle was updated. Production scale is now sufficient to meet the needs of clinical practice. In a pharmacological study numerous models and indicators showed that (–)clau is the active enantiomer, while (+)clau is inactive and elicits greater toxicity than (–)clau. The principal pharmacological effects of (–)clau are to increase cognition, demonstrated in ten models of memory impairment, as well as to inhibit β-amyloid (Aβ) toxicity, blocking neurofibrillary tangle formation by inhibiting the phosphorylation of tau protein. This anti-dementia effect is characterized by increased synaptic plasticity both in efficacy and in structure and provides new support for the theory that synaptic loss is the main cause of dementia. (–)Clau is considered to be a promising drug candidate for treatment of Alzheimer׳s disease and other neurodegenerative disorders. |
| publisher |
Elsevier |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629111/ |
| _version_ |
1613495957221015552 |