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 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.

This review summarizes the latest research advance of synthetic (–)clausenamide, one of the optical isomers of clausenamide isolated from Clausena lansium. It is a new type anti-dementia agent, characteristic by improved learning and memory in normal and memory impairment rodents, increased synaptic plasticity in both efficacy and structure, and decreased apoptosis with high phosphorylation of tau protein. Owing to this multi-target effect, the low toxicity and unique mechanism of action suggests that it is a promising drug for treatment of neurodegenerative diseases and many kinds of memory impairment .Figure optionsDownload as PowerPoint slide