How Drugs Work: Disease Prevention

The design and synthesis of new drugs today is greatly facilitated by scientists’ improved understanding as to how such compounds work in the body. Researchers have long known that most drugs that cure disease do so by killing the microorganisms that cause such diseases. They now have, in many cases, a very detailed and specifi c understanding as to how that process occurs. Research on HIV infection and AIDS (acquired immunodefi ciency syndrome) is a good example. In 1983, two researchers, Luc Montagnier in France and Robert Gallo in the United States, reported that AIDS is caused by a particular type of virus that was later given the name human immunodefi ciency virus (HIV). Over the next decade, teams of researchers in many countries discovered the mechanism by which HIV causes the symptoms of AIDS.

The fi rst step in that process occurs when a person is exposed to HIV (usually through sexual contact or transfer of blood from an infected to a healthy person). HIV travels through the bloodstream until it comes into contact with certain types of white blood cells that contain proteins known as CD4 (cluster designation 4) receptor sites on their surface. The virus then attaches itself to the CD4 receptor and injects a protein (called the p24 protein) into the host cell’s interior. The p24 protein carries the genetic information that
controls reproduction of HIV.

Once installed inside the host cell, the p24 protein attaches itself to and takes over control of the cell’s own DNA. The HIV genetic code begins to function within the host cell, ordering it to produce multiple copies of itself (the virus). The host cell then becomes fi lled with new copies of the HIV, bursts open, releases the viruses into the bloodstream, and dies. Each of the new viruses thus produced then fi nds another CD4 host cell, and the whole process of reproduction is repeated.

Before scientists understood this process, about the only way they had of treating the symptoms of AIDS was a trial-and-error search for chemicals that appeared to have success in curing or slowing down the disease. Once the mechanism of infection was understood, however, they had a more rational method of looking for drugs with which to treat the disease. Their challenge was to fi nd one or more chemicals that would interrupt the series of steps by which the virus operates (attaching itself to the surface of the cell, injecting its p24 protein into the cell, and initiating replication within the host cell).
In fact, various researchers looked for a variety of chemical compounds that acted at one or another of these stages of infection. The best solution that researchers have so far discovered involves the use of a type of drug known as an antiretroviral agent, that is, a chemical that interferes with the process by which the p24 protein takes over the host cell’s own system of replication and reproduction. Many people who are infected with HIV are now able to live reasonably normal lives because they have access to an “AIDS cocktail” that contains some combination of three such antiretroviral substances.

Another example of how drugs kill disease-causing microorganisms is the action of sulfa drugs on bacteria. Normally, a bacterium requires a compound known as para-aminobenzoic acid (PABA) in order to make a second compound, folic acid, as shown in the diagram below. Folic acid, in turn, is used to catalyze the production of nucleic acids that become part of a bacterium’s mechanism for manufacturing new proteins and reproducing its own DNA.

The structure of sulfa drug molecules, however, is very similar to that of the PABA molecule. Compare the structure of sulfanilamide, in part 2 of the diagram, with that of PABA. Notice how easily the sulfanilamide molecule can substitute for the PABA molecule in the synthesis of the bacterium’s folic acid. The problem for the bacterium, however, is that folic acid produced from a sulfa drug molecule is different from one produced from a PABA molecule. The difference is great enough that the altered form of folic acid is unable to catalyze the synthesis of DNA, and the bacterium’s metabolic process is disrupted.

Unable to grow and reproduce, members of the bacterial colony die and the infection that they cause is successfully treated. Understanding the mechanisms by which normal body functions occur, how disease develops, and how drugs fi ght disease is now fundamental to the development of new drugs. This understanding allows researchers to develop new chemical compounds that interfere with biochemical changes that result in disease and death.


by Umaee
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