[A new look at the mechanism of action of antibiotics of the tetracycline series. Tetracyclines as components of radical-generating systems].
Tetracyclines were shown to be able to form radical-generating systems and to affect biological structures at the account of the radical form generation. The radical-generating systems were found to be based on the phenomenon revealed in this study that the tetracyclines catalyzed oxidation of ferrous oxide by oxygen after its binding by these compounds. In the presence of ascorbate the radical formation with the involvement of oxygen could be continuous and accompanied by reduction of ferrous oxide by ascorbate in complex with tetracyclines and its subsequent oxidation as well induced by them. Ca2+ and Mg2+ forming complexes with tetracyclines had no impact on the radical formation. In complex with tetracyclines the ions did not interfere with the tetracycline ability to catalyze oxidation of ferrous oxide after its binding by these compounds. A notion of two functional centres characteristic of tetracyclines was formulated. One of them (chelating) provided the tetracycline binding to Mg2+ and Ca2+ e.g. in ribosomes and the other (toxic) affected the surrounding biological structures by the radical formation.
Iu M
IuM
Petrenko
D001205:Ascorbic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D005296:Ferrous Compounds / Q000378:metabolism; D005609:Free Radicals; D008274:Magnesium / Q000378:metabolism; D010084:Oxidation-Reduction; D013053:Spectrophotometry; D013753:Tetracycline Resistance / Q000502:physiology*; D013754:Tetracyclines / Q000494:pharmacology*
D005296:Ferrous Compounds; D005609:Free Radicals; D013754:Tetracyclines; C034236:ferrous oxide; D008274:Magnesium; D001205:Ascorbic Acid; D002118:Calcium
Novyĭ vzgliad na mekhanizm deĭstviia antibiotikov tetratsiklinovogo riada. Tetratsikliny kak komponent radikal-generiruiushcheĭ sistemy.