Preface [Hot topic:Natural Products as an Inexhaustible Source for Drug Discovery (Guest Editor: Wei-Min Dai)]

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Abstract:

Natural products are the valuable source of structurally diverse compounds which possess therapeutic potential for treatment of human diseases. Many of the clinically used therapeutic agents are of natural products origin, used either in the naturally occurring forms or as the derivatives or analogs after structural optimization. The influence of natural products upon drug discovery has been well recognized and documented. Natural products have been the source of inspiration to drug discovery and are believed to continue playing an important role in future. It is the aim of this special issue on Natural Products as an Inexhaustible Source for Drug Discovery to illustrate the successful examples of modern drugs derived from natural products and to highlight new trends in drug lead discovery and molecular target information mining based on the structural diversity of natural products.

Selection of the reviews for this special issue of Current Medicinal Chemistry was made largely based on the topics of invited lectures delivered at The Third International Symposium for Chinese Medicinal Chemists (ISCMC-2002) held during December 28-31, 2002 at HKUST, Hong Kong SAR, China. The first two reviews highlight the contribution of traditional Chinese medicine (TCM) to modern treatment of disease. The comprehensive review by Y. Li and Y.-L. Wu covers the updated knowledge and progress on chemistry, pharmacology and mode of action of the antimalarial herbal principle, Qinghaosu (Artemisinin). In particular, recent results on molecular targets of Qinghaosu action were presented as well as medicinal applications of Qinghaosu and derivatives other than the antimalarial drug. Huperzine A, an acetylcholinesterase inhibitor, is another excellent example of modern drug originated from TCM for treatment of the Alzheimer's disease. The updated review by D. Bai et al. covers recent progress made during 1999-2002 in clinical, pharmacological and chemical studies on Huperzine A with an emphasis on structural biological advancement with X-ray crystallography and molecular modelling studies on the complex of Huperzine A with acetylcholinesterase.

The third review by X. Hao et al. summaries a systematic study on the chemical principles of Spiraea japonica complex consisting of seven varieties from the Yunnan Province of China. The results form the basis for a chemotaxonomy study on the complex. Moreover, some diterpene alkaloids were revealed to exhibit promising anti-inflammation, anti-platelet aggregation and neuroprotective activities. The fourth review on enediyne prodrugs by W.-M. Dai illustrates an example of drug design inspired by the mode of action of natural products. A unique strategy toward in situ formation of 10-membered ring enediynes was demonstrated via rearrangement of an allylic double bond, supported by the biological results and LC-MS analysis of the reaction products.

Molecular structural diversity has becoming a major concern in drug lead discovery and optimization in recent years. Combinatorial libraries are required to possess natural products-like structural elements for increasing lead hints rate and drugable compounds. The following two reviews outline the state-of-the-art of chemical and biological combinatorial synthesis of structurally diverse compounds of natural products relevance. The team of Z. Yang et al. presents an excellent review on the metal-catalyzed carbon-carbon bond formation reactions applied to the diversity-oriented synthesis of natural product scaffolds using solid phase combinatorial chemistry. Valuable know-hows on selection of synthetic strategy and development of synthetic chemistry are provided. The review by B. Shen et al. highlights the recent advancement in enediyne biosynthesis covering the methodologies developed, the findings achieved so far, and more excitingly, the opportunities for a combinatorial biosynthesis of novel enediynes.

The final review by H. Jiang et al. demonstrates the power of computational chemistry methodology applied to drug lead discovery and molecular target information mining. The virtual screening approach using natural product database takes the advantage of molecular docking and structural diversity of natural products, in particular the knowledge of active chemical principles and associated medicinal applications of TCM. Successful examples and the methodologies used are outlined.

It is hoped that the scientists involved in natural products and the related research fields will find the selection of these reviews, covering from traditional medicinal chemistry methodologies to new frontiers in drug discovery, is beneficial and informative. I would like to thank the authors for their valuable contributions to this special issue. I also would like to dedicate this issue to Prof. Wei-Shan Zhou, a pioneering practitioner in the chemistry of Qinghaosu, of Shanghai Institute of Organic Chemistry, The Chinese Academy of Sciences, on the occasion of his 80th birthday.

Document Type: Book Review

DOI: http://dx.doi.org/10.2174/0929867033456693

Affiliations: Department of Chemistry The Hong Kong University of Science and Technology Clear Water Bay, Kowloon Hong Kong SAR, China

Publication date: November 1, 2003

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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