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

This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003. In the case of all approved agents the time frame has been extended to include the 251/2 years from 01/1981 to 06/2006 for all diseases worldwide and from 1950 (earliest so far identified) to 06/2006 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a “natural product mimic” or “NM” to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 155 small molecules, 73% are other than “S” (synthetic), with 47% actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the antiinfective area ...

/pdf/natural-products-as-sources-of-new-drugs-over-the-last-25-24stxjn5tu.pdf

Natural Products as Sources of New Drugs over the Last 25 Years

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

Marine natural products.

This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012. In the case of all approved therapeutic agents, the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide. As mentioned in the 2012 review, we have continued to utilize our secondary subdivision of a “natural product mimic”, or “NM”, to join the original primary divisions and the designation “natural product botanical”, or “NB”, to cover those botanical “defined mixtures” now recognized as drug entities by the U.S. FDA (and similar organizations). From the data presented in this review, the utilization of natural products and/or their novel structures, in order to discover and develop the final drug entity, is still alive and well. For example, in the area of cancer, over t...

Natural Products as Sources of New Drugs from 1981 to 2014

This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved therapeutic agents, the time frame has been extended to cover the 30 years from January 1, 1981, to December 31, 2010, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2010 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a “natural product mimic” or “NM” to join the original primary divisions and have added a new designation, “natural product botanical” or “NB”, to cover those botanical “defined mixtures” that have now been recognized as drug entities by the FDA and similar organizations. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 175 small molecules, 131, or 74...

/pdf/natural-products-as-sources-of-new-drugs-over-the-30-years-4p9j38phh8.pdf

Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010

Quantitation of the anti-HIV alkaloids michellamines A and B by high pressure liquid chromatography

HTI-286 (Taltobulin), A Synthetic Analog of the Antimitotic Natural Product Hemiasterlin

The multiplicity of natural product structures produced by single-celled microbes from all three domains of life has led to very significant numbers of drugs in many human diseases. This chapter demonstrates that even today, approximately 80 years after the seminal work on penicillin, the microbial world is still a cornucopia of novel structures, but now days, rather than using classical fermentation techniques, the full panoply of genomics, biosynthesis, synthetic modification and serendipity is needed to investigate the incalculable potential of these single-celled organisms so as to unlock their potential as sources of novel scaffolds upon which to “practice the arts of drug discovery and development.”


Keywords:

antiinfectives;
anticholesterolemics;
antitumor;
cryptic clusters;
microbes;
natural products

Microbes to Man: From Soils and the Depths to Drugs

This chapter summarizes the distribution, structural diversity, biological activity, and implications of the occurrence of natural products of the rhizosphere, which are derived from its associated plants and microorganisms. Also discussed is the importance of these and small-molecule rhizodeposition products in a variety of interactions between the rhizosphere organisms. The rhizosphere plays host to rich and diverse communities of bacteria and fungi. The term microbial diversity can be described as the propensity of microorganisms from different taxa, as well as their distribution within the taxa, including the diversity of fungi and bacteria, in microbial communities of a given ecosystem. Comparative studies of bacterial diversity in the rhizosphere and bulk soils involving cultivation-based analysis have revealed a higher population of these microorganisms in the rhizosphere. The rhizosphere is known to host a great diversity of fungal species, and this is strongly influenced by the plant species, its developmental stage, and the soil type.

Natural Products of the Rhizosphere and Its Microorganisms : Bioactivities and Implications of Occurrence

Camptothecin is a potent natural product based anticancer agent isolated from an organic extract of the bark of a Chinese tree, Camptotheca acuminata, Decaisne (Nyssaceae). The chemical identification of camptothecin was first reported in 1966 by Wall et al (1) as a plant alkaloid which showed strong potency against a number of cancer cells derived from leukemia, small cell lung cancer, and colon and rectal cancer. This communication describes the drug discovery and development process of camptothecin from Camptotheca acuminata at the NCI in collaboration with Monroe E. Wall’s group of the Research Triangle Institute and other laboratories facilitated by NCI support. This led to the eventual development of several potent camptothecin analogs, 9-aminocamptothecin, topotecan, irinotecan, and rubitecan, which have been approved for cancer therapy against diverse cancer types including different leukemias and lymphoma, small cell lung carcinoma, colon and rectal cancer, cancer of the central nervous system, renal cell carcinoma, ovarian and breast cancer in humans. Topotecan and irinotecan are also currently used in a wide spectrum of clinical trials in patients with metastatic cancers. The resolution of camptothecin action mechanism targeting topoisomerase I provided vital information in cancer drug action, and stimulated novel and rational cancer drug design and development.

Gordon M. Cragg

Papers

Quantitation of the anti-HIV alkaloids michellamines A and B by high pressure liquid chromatography

HTI-286 (Taltobulin), A Synthetic Analog of the Antimitotic Natural Product Hemiasterlin

Microbes to Man: From Soils and the Depths to Drugs

Natural Products of the Rhizosphere and Its Microorganisms : Bioactivities and Implications of Occurrence

The Camptothecin Experience: From Chinese Medicinal Plants to Potent Anti-Cancer Drugs