Showing papers by "Gordon M. Cragg published in 2002"

Natural products and derivatives as leads to cell cycle pathway targets in cancer chemotherapy.

Abstract: The influence of natural products upon drug discovery in general has been quite impressive; one only has to look at the number of clinically active drugs that are in use in cancer therapy to see how many either are natural products or have a natural pro-duct pharmacophore. What is now becoming quite apparent is that materials from natural sources are excellent probes (indicators) for cellular targets that when modulated, may well have a deleterious effect upon the cycling of a tumor cell through the conventional cell cycle. If the particular target is not expressed in normal cell cycling, then a directed "perturbation" of the tumor cell's cycle may well lead to a novel method of treatment for specific tumor types. In this review we have not attempted to be exhaustive but have given a current overview of how natural products from marine, microbial and plant sources have permitted in-depth analyses of various parts of the cell cycle under varying conditions with the ultimate aims of attempting to "control or perturb" the cycling of tumor cells in a fashion that permits their ultimate removal via cellular death, with a minimum of trauma to the host.

Drugs from nature: past achievements, future prospects

Abstract: Nature has been a source of medicinal agents for thousands of years, and an impressive number of modern drugs have been isolated from natural sources, many based on their use in traditional medicine. The past century, however, has seen an increasing role played by micro-organisms in the production of the antibiotics and other drugs for the treatment of diseases, ranging from bacterial infections to cardiovascular problems and cancer. Much of the world's biodiversity remains unexplored as a source of novel drug leads, and the search for new bioactive agents from natural sources, including extreme environments, will continue. With less than 1% of the microbial world currently known, advances in procedures for microbial cultivation and the extraction of nucleic acids from environmental samples from soil and marine habitats, and from symbiotic and endophytic microbes associated with terrestrial and marine macro-organisms, will provide access to a vast untapped reservoir of genetic and metabolic diversity. These resources will provide a host of novel chemical scaffolds, which can be further developed by combinatorial chemical and biosynthetic approaches to yield chemotherapeutic and other bioactive agents, which have been optimized on the basis of their biological activities. The investigation of these resources requires multi-disciplinary, international collaboration in the discovery and development process.

Antineoplastic agents. 489. Isolation and structures of meliastatins 1-5 and related euphane triterpenes from the tree Melia dubia.

Abstract: The bark of the giant neem tree Melia dubia was found to contain 11 euphane-type triterpenes. Five new compounds, meliastatins 1−5 (1−5), proved to inhibit growth of the P388 lymphocytic leukemia cell line (ED50 1.7−5.6 μg/mL). Four of the others, the previously known methyl kulonate (8), kulinone (9), 16-hydroxybutyrospermol (10), and kulactone (11), were also found to inhibit (ED50 2.5−6.2 μg/mL) the P388 cancer cell line. In addition, two new euphane triterpenes were isolated and named dubione A (6) and dubione B (7). Structures for each of the 11 euphane triterpenes were established by spectral techniques that included HRMS and 2D NMR.

Biodiversity: Medicinals for the millennia

Abstract: Over the millennia, natural products, mainly of plant origin, have been used for the treatment of diseases, and an impressive number of modern drugs have been isolated from natural sources. The past century, however, has seen the increasing importance of microorganisms in the production of the antibiotics and other drugs for the treatment of diseases ranging from bacterial infections to cardiovascular problems and cancer. Much of the world's biodiversity remains unexplored as a source of novel drug leads, and the search for new bioactive agents from natural sources, including extreme environmental niches, Is expanding. In this respect, the majority of microbes have, thus far, defied culture, and advances in procedures for microbial cultivation and the extraction of nucleic acids from environmental samples is providing access to the vast untapped reservoir of microbial genetic and metabolic diversity. Southeast Asia is a region of rich biodiversity with tremendous potential for drug discovery and development. The potential may be optimized through the promotion of national and international collaborations, and the National Cancer Institute (NCI) has established collaborative agreements with organizations In several source countries for the exploration of their natural resources as sources of potential anticancer agents. Collaborative agreements include terms covering factors such as the confidential exchange of data, possibilities for training and technology transfer, patent applications, large-scale resupply of source organisms, and benefit-sharing options.