Combinatorial chemistry: Incomplete Science without the Nature
Statistically speaking, it takes combinatorial chemistry 1 out of 5000 chemical entities in 8 to 12 year process to make it, with costs ranging from $125 to $200 millions [4]. In fact, more than half of the 150 prescription drugs in the market today claim biological origins with annual sale exceeding $40 billion. Of these drugs, 25% are plant derived from the 10% of world that has been looked at. One example of drugs originating from the rain forest is prostatin, which protects cells against AIDS virus. The combinatorial chemistry used to conceivably develop some of the non-biological derivatives is in itself fundamentally based on the naturally occurring processes; only these processes are systematically used to create new leads in drug discovery [15,16].
Let’s face it. Combinatorial chemistry is exceptionally effective in offering wide variety of chemical entities that are derivatives of naturally occurring, pre-existing, working molecules [2,5]. However, it is statistically impossible to completely imitate what the Mother Nature does. The biological/ molecular/ structural diversity that arose out of rain forest is, to say in the least, incredible in its range of multiplicity [1,6,14]. We haven’t even considered or explored any of the new or extreme environmental niches. To quote the words of John H. Cardellina II, “man cannot conceive of all the molecules that Mother Nature has developed”[3]. The molecules found in nature have confronted the challenges of natural selections and overcame them during the molecular evolution. The naturally occurring, working molecules’ level of complexity and diversity is such that even through the combinatorial chemistry, their synthesis cannot be imitated or considered by the existing methods [5]. [Insert anti-tumor compound here]. Even if the naturally occurring proteins of interest may be simple, such as the echistatin (made up of Arg-Gly-Asp) in saw-scaled viper from Africa, their potency is very high [12]. It would have to be by a sheer luck and enormous amount of data that this molecule could possibly be conceived. By studying the existing biological processes, we can find new leads to effective and potent drug discovery.
For those environmentally concerned, those who previously may have had interest in cutting down the rain forest to have more farming have increased appreciation and protection of the forest, motivated by the potential gains from bioprospecting [5,9]. Conservation and preservation of the rain forest also occur through botanists who fight to save rain forests that led to such discovery as prostatin [7]. In issues concerning the patent hold over life forms by the bioprospectors and companies, the U.S. Patent and Trademark Office has recently rescinded the patent holds. This issue arose due to the corruption of biological diversity in the areas of interest by the bioprospectors. In an effort to help the indigenous groups preserve the rain forest diversity as well as the traditional medicine [8], Shaman Pharmaceuticals involve local assistance while the NIH sponsored International Cooperative Biodiversity Groups in partnership with companies like Bristol-Myers Squibb and American Cyanamid. The drug discovery through the rain forest is not just in the areas of botany. Many of the drugs are also attained from animals and insects from the rain forest. Other sources of natural products are sea life and microbes, all of which may not yet be analyzed due to our lack of knowledge [12].
One of the methods used by the combinatorial chemists in imitating the molecular evolution is trial and error. Another term for the trial and error combinatorial chemistry is dry evolution or development. This method alters the cycles of selection and amplification within the molecules, thereby imitating mutations. Although this method may be quick in the laboratorial setting, it lacks even a minimum amount of environmental selection. Environmental selection is important in that efficacy, potency, stability, and selectivity are evolutionarily designed so that the molecules can withstand many survival challenges [11]. It took 15 years for Eli Lilly to develop ProzacÓ [13]. “We think we are clever when we develop combination drug strategies to attack disorders such as cancer and AIDS. But snails discovered this strategy 15 million years ago.”[12] It is through the natural products, which help in finding potential target genes from macromolecules lying along the targeted gene disruption path that we can come to a quick and effective drug discovery.
1. Chemical Ecology-a view from the pharmaceutical-industry
2.The future of bioprospecting.
3. The realities of drug discovery, from an insider’s viewpoint.
4. Industry does a double take on plant-based drugs
5. Ethnobotany and the identification of therapeutic agents from the rain forest
6. Medicines from nature: are natural products still relavent to drug discovery?
7. A botanist fights to save the Samoan rain forest.
8. The medicine man will see you now.
9. Lust for life (Sierra).
10. Sowing where you reap.
11. Blind Wisdom: evolving drugs.
12. Nature's agents help heal humans - some now take steps to reciprocate
13. A hail of Silver Bullets.
14. The Combinatorial Chemistry of Nature.
15.Combinatorial Chemistry and new Drugs.
16.Doing it Nature's way.
17.Biotech's secret Garden
HomeWhat is Combinatorial Chemistry?
-- Solid Phase Synthesis
-- Future Applications of Combinatorial ChemistryMedicines Derived from Combinatorial Chemistry
The Value of The Rainforests
The Fate of the RainforestMedicines Discovered from rainforest Plants