There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.

Plant Products as Antimicrobial Agents

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

This critical review provides an overall survey of the basic concepts and up-to-date literature results concerning the very promising use of gold nanoparticles (AuNPs) for medicinal applications. It includes AuNP synthesis, assembly and conjugation with biological and biocompatible ligands, plasmon-based labeling and imaging, optical and electrochemical sensing, diagnostics, therapy (drug vectorization and DNA/gene delivery) for various diseases, in particular cancer (also Alzheimer, HIV, hepatitis, tuberculosis, arthritis, diabetes) and the essential in vitro and in vivo toxicity. It will interest the medicine, chemistry, spectroscopy, biochemistry, biophysics and nanoscience communities (211 references).

Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity

Introduction Gordon M. Cragg, David G. I. Kingston, and David J. Newman Camptothecin and Its Analogs Nicolas J. Rahier, Craig J. Thomas, and Sidney M. Hecht The Discovery and Development of the Combretastatins Kevin G. Pinney, George R. Pettit, Mary Lynn Trawick, Christopher Jelinek, and David J. Chaplin Homoharringtonine and Related Compounds Hideji Itokawa, Yukio Hitotsuyanagi, and Kuo-Hsiung Lee Podophyllotoxins and Analogs Kuo-Hsiung Lee and Zhiyan Xiao Taxol and its Analogs David G. I. Kingston The Vinca Alkaloids Fanny Roussi, Francoise Gueritte, and Jacques Fahy The Bryostatins David J. Newman The Isolation, Characterization, and Development of a Novel Class of Potent Antimitotic Macrocyclic Depsipeptides: The Cryptophycins Rima S. Al-awar and Chuan Shih Chemistry and Biology of the Discodermolides, Potent Mitotic Spindle Poisons Sarath P. Gunasekera and Amy E. Wright The Dolastatins: Novel Antitumor Agents from Dolabella auricularia Erik Flahive and Jayaram Srirangam Ecteinascidin-743 (Yondelis(R)), Aplidin(R), and Irvalec(R) Carmen Cuevas, Andres Francesch, Carlos M. Galmarini, Pablo Aviles, and Simon Munt Discovery of E7389, a Fully Synthetic Macrocyclic Ketone Analog of Halichondrin B Melvin J. Yu, Yoshito Kishi, and Bruce A. Littlefield HTI-286 (Taltobulin), A Synthetic Analog of the Antimitotic Natural Product Hemiasterlin Raymond J. Andersen, David E. Williams, Wendy K. Strangman, and Michel Roberge The Actinomycins Anthony B. Mauger and Helmut Lackner Anthracyclines Federico-Maria Arcamone Ansamitocins (Maytansinoids) Tin-Wein Yu, Heinz G. Floss, Gordon M. Cragg, and David J. Newman Benzoquinone Ansamycins Kenneth M. Snader Bleomycin Group Antitumor Agents Sidney M. Hecht Biochemical and Biological Evaluation of (+)-CC-1065 Analogs and Conjugates with Polyamides Rohtash Kumar and J. William Lown Epothilone, a Myxobacterial Metabolite With Promising Antitumor Activity Gerhard Hofle and Hans Reichenbach Enediynes Philip R. Hamann, Janis Upeslacis, and Donald B. Borders The Mitomycins William A. Remers Staurosporines and Structurally Related Indolocarbazoles as Antitumor Agents Michelle Prudhomme Combinatorial Biosynthesis of Anticancer Natural Products Steven G. Van Lanen and Ben Shen Developments and Future Trends in Anticancer Natural Products Drug Discovery Gordon M. Cragg and David J. Newman Index

Anticancer Agents from Natural Products

Nanotechnology applied to biological problems represents an emerging field with the potential to offer extremely sensitive diagnostics and targeted cancer therapies. However, to achieve these goals, nanoparticle delivery systems must outwit the many barriers that are intrinsic to the body's defenses, as well as those that develop during the growth and progression of tumors. The science is advancing and, for example, true nanoscale tumor-targeted drug delivery vectors are now able to reduce the likelihood of opsonization in the bloodstream and uptake by the reticuloendothelial system. Other advances hold promise for delivering multiple therapeutic agents to non-homogeneous populations of cancer cells in solid tumors. We briefly summarize herein our attempts to build such multifunctional nanotherapeutics using colloidal gold nanoparticles. Specifically we discuss the development of colloidal gold-based drugs that are designed to target the delivery of TNF and paclitaxel to solid tumors. Drug Dev. Res. 67:47–54, 2006. © 2006 Wiley-Liss, Inc.

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Colloidal gold nanoparticles: a novel nanoparticle platform for developing multifunctional tumor‐targeted drug delivery vectors

Natural products continue to provide a diverse and unique source of bioactive lead compounds for drug discovery, but maintaining their continued eminence as source compounds is challenging in the face of the changing face of the pharmaceutical industry and the changing nature of biodiversity prospecting brought about by the Convention on Biological Diversity. This review provides an overview of some of these challenges and suggests ways in which they can be addressed so that natural products research can remain a viable and productive route to drug discovery. Results from International Cooperative Biodiversity Groups (ICBGs) working in Madagascar, Panama, and Suriname are used as examples of what can be achieved when biodiversity conservation is linked to drug discovery.

Modern Natural Products Drug Discovery and its Relevance to Biodiversity Conservation

Recent studies have shown that paclitaxel leads to activation of Raf-1 kinase and have suggested that this activation is essential for bcl-2 phosphorylation and apoptosis. In the present study, we demonstrate that, in addition to paclitaxel, other agents that interact with tubulin and microtubules also induce Raf-1/bcl-2 phosphorylation, whereas DNA-damaging drugs, antimetabolites, and alkylating agents do not. Activation of Raf-1 kinase by paclitaxel is linked to tubulin polymerization; the effect is blunted in paclitaxel-resistant cells, the tubulin of which does not polymerize following the addition of paclitaxel. In contrast, vincristine and vinblastine, drugs to which the paclitaxel-resistant cells retain sensitivity were able to bring about Raf-1 phosphorylation. The requirement for disruption of microtubules in this signaling cascade was strengthened further using paclitaxel analogues by demonstrating a correlation between tubulin polymerization, Raf-1/bcl-2 phosphorylation, and cytotoxicity. Inhibition of RNA or protein synthesis prevents Raf-1 activation and bcl-2 phosphorylation, suggesting that an intermediate protein(s) acts upstream of Raf-1 in this microtubule damage-activating pathway. A model is proposed that envisions a pathway of Raf-1 activation and bcl-2 phosphorylation following disruption of microtubular architecture, serving a role similar to p53 induction following DNA damage.

https://cancerres.aacrjournals.org/content/canres/57/1/130.full.pdf

Raf-1/bcl-2 Phosphorylation: A Step from Microtubule Damage to Cell Death

The structures of over 350 taxane diterpenoids are classified and presented with information on their plant source, yield, melting point, and optical activity. The biotransformations and biosynthesis of the taxoids are also reviewed.

David G. I. Kingston

Papers

Anticancer Agents from Natural Products

Colloidal gold nanoparticles: a novel nanoparticle platform for developing multifunctional tumor‐targeted drug delivery vectors

Modern Natural Products Drug Discovery and its Relevance to Biodiversity Conservation

Raf-1/bcl-2 Phosphorylation: A Step from Microtubule Damage to Cell Death

The taxane diterpenoids