On the mechanism of action of tetracycline antibiotics

It was found that low oxytetracycline (OTC) concentrations inhibited malic dehydrogenase (MDH) and lactic dehydrogenase (LDH) inStaphylococcus aureus andEscherichia coli (1–5 μg/ml for MDH and 10 μg/ml for LDH). Inhibition of these enzymes occurred almost instantaneously and could be demonstrated after 3–4 minutes. No MDH activity was found in OTC-resistant variants of these microorganisms, but LDH activity was not lowered. The inhibitory effect of OTC is specific for bacterial MDH and LDH. The same enzymes of mammalian origin are not inhibitedin vitro even by high OTC concentrations (100 μg/ml).     

Free radical mechanism of action of pyrimido-triazine antibiotics

EPR spectra of anion radicals were recorded as a result of chemical or enzymatic reduction at various pH of the pyrimido-triazine antibiotics. These anion radicals easily form superoxide radicals in the presence of oxygen. It is supposed that a higher selectivity of reumycin action is due to difference in the redox potentials of the neutral and ionized antibiotic forms. A possibility of enhance the reumycin potency may involve the pH lowering inside the tumor cells - for example, by glucose injections.     

Chemical biology of tetracycline antibiotics.

For more than half a century, tetracycline antibiotics have been used to treat infectious disease. However, what once used to be a commonly prescribed family of antibiotics has now decreased in effectiveness due to wide-spread bacterial resistance. The chemical scaffold of the tetracyclines is a versatile and modifiable structure that is able to interact with many cellular targets. The recent availability of detailed molecular interactions between tetracycline and its cellular targets, along with an understanding of the tetracycline biosynthetic pathway, has provided us with a unique opportunity to usher in a new era of rational drug design. Herein we discuss recent findings that have clarified the mode of action and the biosynthetic pathway of tetracyclines and that have shed light on the chemical biology of tetracycline antibiotics.