CHEMOTHERAPEUTIC AGENTS

Chemotherapeutic agents are substances that can be used internally to control infectious disease. The key requirement for a successful chemotherapeutic agent is selective toxicity, the ability to inhibit microorganisms without affecting the body. Many successful chemotherapeutic agents act as competitive inhibitors of an essential growth factor. The sulfa drugs, for instance, are growth factor analogs, substances structurally similar to the growth factor but different enough that they cannot perform the same function in the cell. The sulfa drug sulfanilamide is an analog of para-amino benzoic acid (PABA) that actually forms part of the vitamin folic acid. Thus bacteria that synthesize their own folic acid incorporate sulfanilamide rather than PABA and folic acid synthesis is blocked. This drug acts selectively against bacteria and not mammals because bacteria synthesize their own folic acid whereas mammals must obtain the vitamin prefabricated in their diet. Analogs are known for various vitamins, amino acids, purines and pyrimidines.

Antibiotics are a special class of chemotherapeutic agents. Antibiotics are chemical substances that are produced by certain microorganisms that are active against other microorganisms; they are natural products rather than synthetic chemicals. The sensitivity of microorganisms to antibiotics varies. Gram-positive bacteria are usually more sensitive to antibiotics than Gram-negative bacteria. An antibiotic that acts on both Gram positive and Gram-negative bacteria is called a broad spectrum antibiotic. Those that are effective against a single group of microorganisms are narrow spectrum antibiotics.

Most antibiotics act by interfering with some aspect of the bacteria's metabolism, such as the synthesis of the cell wall, DNA replication, transcription, or translation. Because viruses do not have cell walls or cytoplasm, most antibiotics are completely ineffective against them. And, since viruses depend on the host cell for most aspects of viral replication, it is difficult to inhibit viral replication without at the same time affecting the host cell itself. There are only a few substances that are effective against a limited number of viruses. One example is rifamycin, which is an inhibitor of the RNA polymerase used in bacteria but not in eukaryotes. The RNA polymerase found in the pox viruses is also inhibited by rifamycin, so it is an effective antiviral agent against any of the these viruses though it is ineffective against the wide range of other viruses that infect animal cells. Another interesting chemical is azidothymidine (AZT), an inhibitor of retroviruses such as the HIV virus. AZT is a derivative of the nucleoside deoxythymidine and lacks the 3' hydroxyl group. AZT blocks the synthesis of cDNA by reverse transcriptase; AZT moves in wherever a thymine would belong, but since there is no 3' -OH group the next nucleotide specified cannot be joined to it. (Remember, nucleic acids synthesis can only proceed from 5' to 3'.)