Current Organic Chemistry - Volume 10, Issue 8, 2006

The 2006 Natural Product Chemistry issue of Current Organic Chemistry contains four contributions covering different themes. One of these involves methodology, in which Potterat and Hamburger look at approaches to the localization and characterization of bioactivity. New technologies and concepts have been introduced over the last few years and these are the subject of this article. Sensitive and rapid methods are required to accelerate the discovery of new plant-based drugs and provide lead compounds. These methods include HPLC-based bioassays, molecular imprinted polymers, biosensors and chips. Bioassays for the screening of natural products are also presented in a review of natural inhibitors of acetylcholinesterase. This enzyme degrades acetylcholine and as cholinergic deficit is associated with the cognitive impairments observed in Alzheimer's disease, inhibitors of the enzyme are at present actively being sought in order to find new therapeutics for the management of this widespread affliction of elderly people. Many alkaloids with an effect on the enzyme have been discovered but there is also a need to find non-alkaloidal natural products which show inhibition as these might have fewer side effects. Some of the compounds isolated are, in fact, more active than the currently used drugs, such as galanthamine from Galanthus nivalis (Amaryllidaceae). The third contribution is a review by Brahmachari and Gorai of recently reported flavones and flavonols from plant sources during the period 1999 to 2004. Many of these have interesting biological and pharmacological activities. Finally, Gao reviews metabolites from Chinese fungi. Chinese higher fungi, apart from certain species such as Ganoderma lucidum (Ganodermataceae), have received little attention and previous research has been confined mainly to several traditionally-used medicinal higher fungi, from which the number of secondary metabolites so far discovered is only about 150. China is one of the richest resources of fungi in the world, with approximately 10,000 species of higher fungi. Edible and inedible mushrooms represent about 600 and 500 species, respectively, including some 100 toxic species. Higher fungi have a large and diversified variety of secondary metabolites, as exemplified in this review. I would like to express my sincere thanks to all contributors in this volume for the excellent reviews of natural product research that they have produced.

Various natural products, such as physostigmine, have long been recognized as inhibitors of the enzyme acetylcholinesterase. Since the recent approval of galanthamine for the treatment of Alzheimer's disease by the blockage of acetylcholine degradation, attempts to find other inhibitors of the enzyme have multiplied, leading to promising candidates such as huperzine A. In this review, a listing is presented of natural product inhibitors, both alkaloid and nonalkaloid in origin. These have been isolated from plant, animal and microbial sources. Details of current testing methods on cholinesterases are given, including solution assays and screening techniques by TLC and HPLC.

The chemical constituents produced by Chinese higher fungi, including thirty two basidiomycete and six ascomycete species, have been investigated in the past decades. A variety of new secondary metabolites associated with diverse structural types of terpenoids, steroids, sphingolipids, perylenequinones, p-terphenyls, pyranones, and heterocyclic compounds, which exhibited antitumor, anti-inflammatory, cytotoxic, enzyme inhibitory, antiviral, neuritogenic, antibiotic, and other activities, have been discovered. Recent progress in the structures and interesting biological properties of compounds isolated from these higher fungi is discussed in this review.

The present review deals with recently reported novel natural flavones and flavonols (mid-1999 to early 2004), along with various biological and pharmacological activities as exhibited by these important groups of flavonoids. The present resumé lists 252 new naturally occurring flavones and flavonols reported during the period. Natural distribution by plant family of the flavonoids is considered; a variety of plant species belonging to fifty-two different plant families is mentioned as their natural sources. Therapeutic efficacies of these constituents are also cited. The review covers 231 references.

Effective methods for localization and characterization of bioactivity are a cornerstone for natural product based drug discovery efforts. Over the last decade, a wealth of new technologies and conceptual approaches for bioactivity screening have emerged. These developments are reviewed under the perspective of their applicability in the field of natural products discovery. The methods discussed here include bioautography, HPLC-based activity profiling, HPLC-based on-flow bioassays, assays based on capillary electrophoresis, molecular imprinted polymers, various MSand NMR-based methods, biosensors, and chip-based technologies for affinity separation and expression profiling. Selected examples illustrate the potential and limitations of the different approaches for contemporary natural products lead discovery.