Cephalotaxus Alkaloids
| Autor: | Joëlle Pérard-Viret, Rana Alsalim, Jacques Royer, Françoise Dumas, Laith Quteishat |
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| Přispěvatelé: | Chimie Organique, Médicinale et Extractive et Toxicologie Expérimentale (COMETE - UMR 8638), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Molécules bioactives, conception, isolement et synthèse (MBCIS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Academic Press Elsevier, Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Paris Descartes - Paris 5 (UPD5) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
biology
010405 organic chemistry Stereochemistry Chemistry [CHIM.ORGA]Chemical Sciences/Organic chemistry Alkaloid Harringtonine Cephalotaxus [CHIM.THER]Chemical Sciences/Medicinal Chemistry 010402 general chemistry biology.organism_classification 01 natural sciences Antiparasitic agent 3. Good health 0104 chemical sciences Benzazepine chemistry.chemical_compound Cephalotaxaceae Homoharringtonine Cephalotaxus Alkaloids |
| Zdroj: | The Alkaloids Academic Press Elsevier. The Alkaloids, 78, pp.205-352, 2017, The Alkaloids, ⟨10.1016/bs.alkal.2017.07.001⟩ |
| DOI: | 10.1016/bs.alkal.2017.07.001⟩ |
| Popis: | International audience; Cephalotaxus alkaloids represent a family of plant secondary metabolites known for60 years. Significant activity against leukemia in mice was demonstrated for extractsof Cephalotaxus. Cephalotaxine (CET) (1), the major alkaloid of this series was isolatedfrom Cephalotaxus drupacea species by Paudler in 1963. The subsequent discovery ofpromising antitumor activity among new Cephalotaxus derivatives reported by Chinese,Japanese, and American teams triggered extensive structure elucidation and biologicalstudies in this family. The structural feature of this cephalotaxane family relies mainly onits tetracyclic alkaloid backbone, which comprises an azaspiranic 1-azaspiro[4.4]nonaneunit (rings C and D) and a benzazepine ring system (rings A and B), which is linked by itsC3 alcohol function to a chiral oxygenated side chain by a carboxylic function alpha to atetrasubstituted carbon center. The botanical distribution of these alkaloids is limited tothe Cephalotaxus genus (Cephalotaxaceae). The scope of biological activities ofthe Cephalotaxus alkaloids is mainly centered on the antileukemic activity of homoharringtonine (HHT) (2), which in particular demonstrated marked benefits in thetreatment of orphan myeloid leukemia and was approved as soon as 2009 by EuropeanMedicine Agency and by US Food and Drug Administration in 2012. Its exact mechanismof action was partly elucidated and it was early recognized that HHT (2) inhibitedprotein synthesis at the level of the ribosome machinery. Interestingly, after a latencyperiod of two decades, the topic of Cephalotaxus alkaloids reemerged as a prolificsource of new natural structures. To date, more than 70 compounds have beenidentified and characterized. Synthetic studies also regained attention during thepast two decades, and numerous methodologies were developed to access the firstsemisynthetic HHT (2) of high purity suitable for clinical studies, and then high gradeenantiomerically pure CET (1), HHT (2), and analogs. |
| Databáze: | OpenAIRE |
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