Chemistry 1020-Lecture 23-Notes
Chapter 11: Designing Drugs and Manipulating Molecules
Chemistry touches many aspects of everyday life. It is interesting that the majority of the class listed the chapter on drugs as their highest priority for discussion. Clearly in the approximate two lecture periods we have left we cannot tell you everything you ever wanted to know, but perhaps we can help you make a connection between the fundamental ideas underlying drug action and the chemistry involved in those ideas.
What is a drug? We might define it as a single chemical substance that is an active ingredient in a medicine. Therefore, there is a subtle difference between the term medicine and drug. Some medicines may, in fact, contain several drugs as components. If you search the pharmacy shelves for treatments for cold symptoms, for example, you will find some of the medicines available consisting of several different drugs, each presumed to treat a different aspect of cold symptoms.
In everyday use by the public, the term "drug" had pretty negative connotations. We have reports of "drug dealers", people doing things under the influence of drugs, and athletes screened for the use of "performance enhancing" drugs. We are all used to the slogan aimed at young people"Just say no" to drugs.
Yet drugs, in the form of medicines, have greatly enhanced our quality of life over the last century. We have treatments for many diseases that would earlier have been very debilitating or have led to an early death. We can correct through medication a number of abnormalities in normal functioning of the human body. We have made possible life-saving operations such as heart transplants. So drugs are like the proverbial two-edged sword. There is a good side and a bad side, and only by understanding them and what they do can we hope to harness the good and avoid the bad.
The pharmaceutical industry is a greater than $billion dollar industry that is in the business not only of manufacturing drugs for our use, but in discovering new drugs to treat conditions that have no current treatment, or to improve the efficacy of existing drugs. Some drugs are expensive because the process of developing them is expensive.
Let me cite a local example. For many years the search for a cure for cancer has taken many guises. One of them was the search for new chemical compounds that would preferentially inhibit the growth of cancer cells. Among thousands, maybe millions, of compounds tested by the National Cancer Institute, one was particularly promising. It was obtained from the bark of the Pacific Yew tree, and has been called by several names, perhaps the most recognizable, taxol. From the following chemical structure, you can see that taxol is a very complicated organic molecule:
(Click on the image above to see the structure in 3 dimensions, using the Chime plugin). At first, taxol was a potential drug that no drug company was particularly interested in, especially since the discovery had been through some government supported screening. The National Institutes of Health, which is responsible for funding much of medical research today, had to offer some special incentives for a drug company to take on the job of further testing and producing taxol as a viable anti-cancer drug. Bristol-Myers Squibb obtained the right for exclusive development and sales for a period of some years in return for their investment in the development stages of the drug.
One problem with the drug was the need to cut down Yew trees in order to obtain the bark for extraction. Environmentalists became extremely concerned, since the need for the bark could conceivably lead to destruction of all available Pacific Yew trees.
The needles of the Yew tree make a compound similar to taxol, a compound that can be converted to taxol in a few chemical steps. Professor Robert Holton developed a chemical procedure for this conversion, obtained patent rights to the procedure, and has licensed the procedure to Bristol-Myers Squibb as a means of "semisynthetic" production. Through his licensing, Florida State University has now earned close to 100 million dollars in fees, 4.5% of the gross income from sales of the drug.
This illustration highlights two conclusions:
How do drugs get discovered? Where do they come from? How do they work? These questions are not simply answered. In fact, after a years course in pharmacology, you still wouldnt be experts in all the details involving drug discovery and production and mechanism of drug action.
Lets first look at the variety of things which drugs are used for. One classification of drugs could be done according to the application.
Antibiotics, anti-viral, anti-parasitic
This is by no means a comprehensive summary of drug targets or types. But you can see an underlying principle that the drugs act somehow to affect the chemical reactions occurring in living cells.
Two of the principle targets for drug actions include enzymes and receptors.
Enzymes are large molecules of protein which catalyze chemical reactions in living organisms. Virtually every reaction except proton transfer is enormously accelerated in rate by these specific catalysts, so that the reactions which do occur in the cell depend on what enzymes are there. Enzymes act by having very specific surface binding sites that are complementary to the molecular structure of the compounds which they cause to react (called their substrates). Substrates bind specifically to these surface sites in the process of the reaction. Many drugs act by mimicking the substrate in structure, binding to the specific site on the enzyme, thereby blocking the binding of substrate and inhibiting the reaction.
Receptors are also protein molecules which are imbedded in the membranes of cells. Hormones and other signaling molecules bind to the surface of a receptor, causing a change in the shape of the receptor which is translated to some interaction just inside the cell membrane that activates an enzyme. This process triggers a series of enzymatic reactions inside the cell leading to some change in the metabolism of the cell. Some drugs act by binding to receptors, either producing the effect of the hormone (agonist activity) or blocking the effect of the hormone (antagonist activity).