Chemical Diversity of Natural Products
As above mentioned, combinatorial chemistry was a key technology enabling the efficient generation of large screening libraries for the needs of high-throughput screening. However, now, after two decades of combinatorial chemistry, it has been pointed out that despite the increased efficiency in chemical synthesis, no increase in lead or drug candidates has been reached. This has led to analysis of chemical characteristics of combinatorial chemistry products, compared to existing drugs or natural products. The chemoinformatics concept chemical diversity, depicted as distribution of compounds in the chemical space based on their physicochemical characteristics, is often used to describe the difference between the combinatorial chemistry libraries and natural products. The synthetic, combinatorial library compounds seem to cover only a limited and quite uniform chemical space, whereas existing drugs and particularly natural products, exhibit much greater chemical diversity, distributing more evenly to the chemical space. The most prominent differences between natural products and compounds in combinatorial chemistry libraries is the number of chiral centers (much higher in natural compounds), structure rigidity (higher in natural compounds) and number of aromatic moieties (higher in combinatorial chemistry libraries). Other chemical differences between these two groups include the nature of heteroatoms (O and N enriched in natural products, and S and halogen atoms more often present in synthetic compounds), as well as level of non-aromatic unsaturation (higher in natural products). As both structure rigidity and chirality are both well-established factors in medicinal chemistry known to enhance compounds specificity and efficacy as a drug, it has been suggested that natural products compare favourable to today's combinatorial chemistry libraries as potential lead molecules.
Read more about this topic: Drug Discovery
Famous quotes containing the words chemical, diversity, natural and/or products:
“If Thought is capable of being classed with Electricity, or Will with chemical affinity, as a mode of motion, it seems necessary to fall at once under the second law of thermodynamics as one of the energies which most easily degrades itself, and, if not carefully guarded, returns bodily to the cheaper form called Heat. Of all possible theories, this is likely to prove the most fatal to Professors of History.”
—Henry Brooks Adams (1838–1918)
“We call the intention good which is right in itself, but the action is good, not because it contains within it some good, but because it issues from a good intention. The same act may be done by the same man at different times. According to the diversity of his intention, however, this act may be at one time good, at another bad.”
—Peter Abelard (1079–1142)
“The great man knew not that he was great. It took a century or two for that fact to appear. What he did, he did because he must; it was the most natural thing in the world, and grew out of the circumstances of the moment. But now, every thing he did, even to the lifting of his finger or the eating of bread, looks large, all-related, and is called an institution.”
—Ralph Waldo Emerson (1803–1882)
“But, most of all, the Great Society is not a safe harbor, a resting place, a final objective, a finished work. It is a challenge constantly renewed, beckoning us toward a destiny where the meaning of our lives matches the marvelous products of our labor.”
—Lyndon Baines Johnson (1908–1973)