Wei-Shuo Fang

Bio: Wei-Shuo Fang is an academic researcher from Peking Union Medical College. The author has contributed to research in topics: Paclitaxel & Oleanolic acid. The author has an hindex of 22, co-authored 88 publications receiving 1297 citations. Previous affiliations of Wei-Shuo Fang include Chinese Ministry of Education & Wuhan University.

Structure-activity Relationships of oleanane-and Ursanetype Triterpenoids

Abstract: The chemistry of oleanane-and ursane-type triterpenoids has been actively explored in recent years, and their biological and pharmacological activities of these compounds have been found to span a variety of properties. These include antitumor, anti-viral, anti-inflammatory, hepatoprotective, gastroprotective, antimicrobial, antidiabetic, and hemolytic properties as well as many others. This review summarizes the isolation and structure modifications of these triterpenoids as well as the biological and pharmacological activities discovered in the past ten years, with an emphasis on their structure-activity relationships.

Medicinal chemistry of bioactive natural products

Abstract: Preface. Contributors. 1 The Chemistry and Biology of Epothilones-Lead Structures for the Discovery of Improved Microtubule Inhibitors (Karl-Heinz Altmann). 1.1. Introduction. 1.2. Biological Effects of Epo B. 1.3. Epothilone Analogs and SAR Studies. 1.4. Pharmacophore Modeling and Conformational Studies. 1.5. Epothilone Analogs in Clinical Development. 1.6. Conclusions. Acknowledgments. References. 2 The Chemistry and Biology of Vancomycin and Other Glycopeptide Antibiotic Derivatives (Roderich D. Su ssmuth). 2.1. Introduction. 2.2. Classification of Glycopeptide Antibiotics. 2.3. Mode of Action. 2.4. Glycopeptide Resistance. 2.5. Biosynthesis. 2.6. Total Synthesis. 2.7. Glycopeptides as Chiral Selectors in Chromatography and Capillary Electrophoresis. 2.8. Structural Modifications of Glycopeptide Antibiotics and Structure Activity Relationship (SAR) Studies. Acknowledgment. References. 3 Structure Modifications and Their Influences on Antitumor and Other Related Activities of Taxol and Its Analogs (Wei-Shuo Fang, Qi-Cheng Fang, and Xiao-Tian Liang). 3.1. Discovery and Research and Development of Taxol. 3.2. Paclitaxel Analogs Active Against Normal Tumor Cells. 3.3. Exploration on Mechanism of Paclitaxel Related to Tubulin Binding and Quest for Its Pharmacophore. 3.4. Natural and Semisynthetic Taxoids Overcoming Multidrug Resistance (MDR). 3.5 Design, Synthesis and Pharmacological Activity of Prodrugs of Paclitaxel. 3.6 Other Biological Actions of Paclitaxel. 3.7 New Antimicrotubule Molecules Mimicking Action of Paclitaxel. 3.8 Conclusion. Acknowledgments. References. 4 The Overview of Studies on Huperzine A: A Natural Drug for the Treatment of Alzheimer's Disease (Da-Yuan Zhu, Chang-Heng Tan, and Yi-Ming Li). 4.1 Introduction. 4.2. Profiles of HA. 4.3. Plant Resources. 4.4. Pharmacology. 4.5. Clinical Trials. 4.6. Synthesis of HA and Its Analogs. 4.7. Structural Biology. 4.8. ZT-1: New Generation of HA AChE. Abbreviations. References. 5 Qinghaosu (Artemisinin)-A Fantastic Antimalarial Drug from a Traditional Chinese Medicine (Ying Li, Hao Huang, and Yu-Lin Wu). 5.1. Introduction. 5.2. Qinghaosu and Qinghao (Artemisia annua L. Composites). 5.3. Reaction of Qinghaosu. 5.4. Chemical Synthesis and Biosynthesis of Qinghaosu. 5.5. Derivatives and Antimalarial Activity. 5.6. Pharmacology and Chemical Biology of Qinghaosu and Its Derivatives. 5.7 Conclusion. References. 6 Progress of Studies on the Natural Cembranoids from the Soft Coral Species of Sarcophyton Genus (Yulin Li, Lizeng Peng, and Tao Zhang). 6.1. Introduction. 6.2. Cembrane-Type Constituents from the Sarcophyton Genus. 6.3. Physiological Action of Sarcophytol A and Sarcophytol B. 6.4. Total Synthesis of the Natural Cembranoids. 6.5. Studies on Novel Macrocyclization Methods of Cembrane-Type Diterpenoids. Acknowledgments. References. 7 Medicinal Chemistry of Ginkgolides from Ginkgo biloba (Kristian Stromgaard). 7.1. Introduction. 7.2. Ginkgolides and the PAF Receptor. 7.3. Ginkgolides and Glycine Receptors. 7.4. Various Effects of Ginkgolides. 7.5. Conclusions and Outlook. Acknowledgment. References. 8 Recent Progress in Calophyllum Coumarins as Potent Anti-HIV Agents (Lin Wang, Tao Ma, and Gang Liu). 8.1. Introduction. 8.2. Anti-HIV-1 Activity of Calophyllum Coumarins. 8.3. Pharmacology of Calanolides. 8.4. Preparation of Calophyllum Coumarins. 8.5. Structure Modification of Calanolides. 8.6. Conclusion. References. 9 Recent Progress and Prospects on Plant-Derived Anti-HIV Agents and Analogs (Donglei Yu and Kuo-Hsiung Lee). 9.1. Introduction. 9.2. Khellactone Coumarin Analogs as Anti-HIV Agents. 9.3. Biphenyl Derivatives as Anti-HIV Agents. 9.4. Triterpene Betulinic Acid Derivatives as Anti-HIV Agents. 9.5. Conclusions. Acknowledgments. References. 10 Recent Progress on the Chemical Synthesis of Annonaceous Acetogenins and Their Structurally Modified Mimics (Tai-Shan Hu, Yu-Lin Wu, and Zhu-Jun Yao). 10.1. Introduction. 10.2. Total Synthesis of Mono-THF Acetogenins. 10.3. Total Synthesis of Bis-THF Acetogenins. 10.4. Total Synthesis of THP-Containing Acetogenins. 10.5. Design and Synthesis of Mimics of Acetogenins. 10.6. Summary. References. Index.

High-level semi-synthetic production of the potent antimalarial artemisinin

Abstract: Saccharomyces cerevisiae is engineered to produce high concentrations of artemisinic acid, a precursor of the artemisinin used in combination therapies for malaria treatment; an efficient and practical chemical process to convert artemisinic acid to artemisinin is also developed. Artemisinin-based combination therapies are the treatment of choice for uncomplicated Plasmodium falciparum malaria, but the supply of plant-derived artemisinin can sometimes be unreliable, causing shortages and high prices. This manuscript describes a viable industrial process for the production of semisynthetic artemisinin, with the potential to help stabilize artemisinin supply. The process uses Saccharomyces cerevisiae yeast engineered to produce high yields of artemisinic acid, a precursor of artemisinin. The authors have also developed an efficient and scalable chemical process to convert artemisinic acid to artemisinin. In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths1. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers2. A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker’s yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid3. Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.

Natural products as leads to anticancer drugs.

Abstract: Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology. Within the sphere of cancer, a number of important new commercialised drugs have been obtained from natural sources, by structural modification of natural compounds, or by the synthesis of new compounds, designed following a natural compound as model. The search for improved cytotoxic agents continues to be an important line in the discovery of modern anticancer drugs. The huge structural diversity of natural compounds and their bioactivity potential have meant that several products isolated from plants, marine flora and microorganisms can serve as “lead” compounds for improvement of their therapeutic potential by molecular modification. Additionally, semisynthesis processes of new compounds, obtained by molecular modification of the functional groups of lead compounds, are able to generate structural analogues with greater pharmacological activity and with fewer side effects. These processes, complemented with high-throughput screening protocols, combinatorial chemistry, computational chemistry and bioinformatics are able to afford compounds that are far more efficient than those currently used in clinical practice. Combinatorial biosynthesis is also applied for the modification of natural microbial products. Likewise, advances in genomics and the advent of biotechnology have improved both the discovery and production of new natural compounds.

Microtubule inhibitors: Differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance

Abstract: Microtubules are important cellular targets for anticancer therapy because of their key role in mitosis. Microtubule inhibitors (MTI) such as taxanes, vinca alkaloids, and epothilones stabilize or destabilize microtubules, thereby suppressing microtubule dynamics required for proper mitotic function, effectively blocking cell cycle progression and resulting in apoptosis. In spite of their antitumor activity, innate or acquired drug resistance to MTIs such as the taxanes is common, limiting their overall clinical efficacy. Further insight into the mechanisms of action of microtubule-targeting drugs has lead to the discovery of novel agents that may provide higher efficacy with limited toxicity and help overcome resistance to conventional MTIs. This review will focus on the different mechanisms of action of MTIs, potential factors related to resistance and tolerability, and will discuss the recent approval as well as the development of new antineoplastic agents.

Metabolic and functional diversity of saponins, biosynthetic intermediates and semi-synthetic derivatives.

Abstract: Saponins are widely distributed plant natural products with vast structural and functional diversity. They are typically composed of a hydrophobic aglycone, which is extensively decorated with functional groups prior to the addition of hydrophilic sugar moieties, to result in surface-active amphipathic compounds. The saponins are broadly classified as triterpenoids, steroids or steroidal glycoalkaloids, based on the aglycone structure from which they are derived. The saponins and their biosynthetic intermediates display a variety of biological activities of interest to the pharmaceutical, cosmetic and food sectors. Although their relevance in industrial applications has long been recognized, their role in plants is underexplored. Recent research on modulating native pathway flux in saponin biosynthesis has demonstrated the roles of saponins and their biosynthetic intermediates in plant growth and development. Here, we review the literature on the effects of these molecules on plant physiology, which collectively implicate them in plant primary processes. The industrial uses and potential of saponins are discussed with respect to structure and activity, highlighting the undoubted value of these molecules as therapeutics.