Biotechnology - Yu.O. Sazykin 2006

Applied Biotechnology
Problems of discovery, development, and application of antibiotics in medical practice
Mechanisms of antibiotic action - Nucleic acid synthesis inhibitors

This group of Antibiotics (including anthracyclines, bleomycin, olivomycin, etc.) comprises A number of DNA-tropic antitumor agents. They inhibit RNA Synthesis, and some suppress the synthesis of both DNA and RNA by binding to DNA (which serves as a template for both METABOLISM/36.html">DNA Replication and Transcription, i.e., RNA synthesis).

Such antibiotics are invariably quite toxic because they bind to DNA of any origin—bacterial, viral, plant, or animal. Their use as cytostatics in oncology is justified by the fact that tumor Cells proliferate (multiply) much faster than normal tissue cells, making the antitumor effect of these antibiotics more pronounced.

In infectious disease clinics, DNA-otropic drugs are generally not used due to their toxicity and the availability of more selectively acting antimicrobial antibiotics.

Inhibitors of nucleic acid synthesis are not limited to DNA-tropic antibiotics. The antibiotic rifampicin, an inhibitor of RNA synthesis, binds not to the DNA template, but to an enzyme—RNA polymerase. Crucially, it binds selectively, targeting only the bacterial enzyme rather than that of animal cells. Rifampicin is used to treat various infections, including tuberculosis, as it can be administered to humans over extended periods without significant toxicity.

Another category of Enzyme Inhibitors involved in the synthesis and metabolism of Nucleic Acids includes the new synthetic antibacterial agents known as fluoroquinolones, which are currently being introduced into clinical practice.

These drugs exhibit a broad antibacterial spectrum. An example is pefloxacin (abactal):

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which primarily targets Gram-negative Bacteria, and norfloxacin (nolicin):

which differs from the former by the absence of a methyl group in the piperazinyl ring and exhibits higher antibacterial activity.

Notably, evidence suggests that fluoroquinolones affect The Development of Cartilage tissue (for this reason, their use in pediatric practice is not recommended). Although they are not products of biotechnological manufacturing, given their practical importance and the feasibility of producing covalently linked cephalosporin-fluoroquinolone conjugates, it is worthwhile to briefly review their MECHANISM OF ACTION.

Fluoroquinolones act as Inhibitors of the enzyme DNA gyrase. The function of this enzyme is to introduce "supercoils" into circular DNA or to "twist" its molecule. This makes the DNA molecule more compact and induces "internal tension": when cleaved by restriction Enzymes, the complementary strands separate rapidly, facilitating the action of DNA and RNA polymerases during DNA replication or transcription (RNA synthesis on a DNA template). DNA gyrase consists of several subunits and catalyzes multiple reactions, including energy-requiring steps for supercoiling DNA. Fluoroquinolones inhibit the function of the so-called subunit A. Bacterial DNA gyrase is classified as a DNA topoisomerase. Fluoroquinolones do not interact with DNA topoisomerases of animal cells.