Post details: The "treasure trove of small molecules" in the natural world

03/28/07

Permalinkby 11:52:15 am, Categories: Literature - Articles, 671 words   English (UK)

The "treasure trove of small molecules" in the natural world

Most of us know that aspirin derives from a naturally occurring chemical, salicylic acid, found in the bark of willow trees. Many of us know that the inhabitants of tropical rainforests are aware of the medicinal properties of a great number of leaves, roots, bark and other natural materials. What few of us realise is just how many of the drugs on pharmacy shelves derive from the natural world. In a review covering the past 60 years, two chemists have concluded that 70% of new drugs (never previously available as commercial products) are either derived from plants and animals or synthesised to mimic the natural product. This statistic is entirely in line with two previous reviews these authors had undertaken.
They write: "the continuing and overwhelming contribution of natural products to the expansion of the chemotherapeutic armamentarium is clearly evident, and as we stated in our earlier papers, much of Nature's "treasure trove of small molecules" remains to be explored, particularly from the marine and microbial environments." They make a particular point about microbially-produced substances: "We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore we consider that this area of natural product research should be expanded significantly."
In a recent entry to this literature blog, a link was made between "systems biology" and design theory. Both lead to the same scientific methodologies. Both emphasise the multidisciplinary character of research, and the importance of holistic (rather than reductionistic) thinking. The review authors have the same approach: "To us, a multidisciplinary approach to drug discovery, involving the generation of truly novel molecular diversity from natural product sources, combined with total and combinatorial synthetic methodologies, and including the manipulation of biosynthetic pathways (so-called combinatorial biosynthesis), provides the best solution to the current productivity crisis facing the scientific community engaged in drug discovery and development."
If the natural world is designed, and if mankind has a legitimate place within this designed world, the finding that natural medicinal products actually work is not surprising. Indeed, positive thoughts about design naturally follow.

Natural Products as Sources of New Drugs over the Last 25 Years
David J. Newman and Gordon M. Cragg
Journal of Natural Products, 70(3), 461-477, 2007. 10.1021/np068054v S0163-3864(06)08054-2

Abstract: 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 being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore we consider that this area of natural product research should be expanded significantly.

See also:
Mother Nature's Medicine Cabinet
Science Daily, March 20, 2007.

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