Current Progresses of Novel Natural Products and Their Derivatives/ Analogs as Anti-Alzheimer Candidates: an Update

Abstract

Alzheimer's disease (AD) is one of the most threatening diseases affecting the aged with high incidence. Though AD has been defined for more than 100 years, it is still incurable. The drugs clinically used for the treatment of this disease, such as acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonist, can only provide a limited therapeutic effect. The need of effective drugs has stimulated the search for new compounds with potential clinical utility. Natural products are rich and unexplored sources for discovering novel leading compounds. Currently, a great number of natural products have been found possessing anti-AD property counteracting different etiological factors of AD. This review will give an update demonstration on the novel anti-AD natural products and their derivatives/analogues, which have been divided into five subgroups according to their different action mechanisms: AChEIs, antioxidants, neuroprotective agents, monoamine oxidase (MAO) inhibitors, and tau hyperphosphorylation inhibitors. We put special emphasis on the findings in the past 5 years. Besides, the drug design strategy as well as the structure-activity relationship of the relevant compounds is also discussed when it is possible.

In silico target fishing and pharmacological profiling for the isoquinoline alkaloids of Macleaya cordata (Bo Luo Hui)

“…According to the pharmacological profiling, some unreported pharmacological performances of M. cordata emerged. In this study, 10 targets linked with neurodegeneration were fished, among which AChE and MAO-B were crucial therapeutic targets in Alzheimer's disease and Parkinson's disease [91][92][93][94].…”

Rational Modification of the Biological Profile of GPCR Ligands through Combination with Other Biologically Active Moieties

“…According to the cholinergic hypothesis , inhibition of ChE increases the amount of ACh in the synaptic cleft and therefore improves cognitive function of patients. Discovery of novel ChE inhibitors are pursued by several groups including our efforts .…”

Territrem and Butyrolactone Derivatives from a Marine-Derived Fungus Aspergillus Terreus

“…Thus, enhancement of the central cholinergic neurotransmission has been regarded as one of the most promising strategies for the symptomatic treatment of AD. Accordingly, acetylcholinesterase (AChE) inhibitors are currently the most effective treatment targets for the design of anti-Alzheimer drug candidates [ 3 ].…”