Tetracycline antibiotics

Abstract

Tetracyclines belong to the first broad-spectrum, well-tolerated, and easy-to-administer antibiotics, which are effective against plague, cholera, typhoid, syphilis, Legionnaire’s disease, and anthrax. Some can also be used to treat malaria, Lyme disease, tuberculosis, Rocky Mountain spotted fever, and leprosy. Humans first encountered these chemical species involuntarily in ancient times, as evidenced from the analysis of bone samples dating back more than 1500 years. Shortly after World War II, they were “rediscovered” at Lederle Laboratories and Pfizer as a result of an intense search for new antibiotics. Their bacteriostatic action is based on the inhibition of protein biosynthesis. Since the structure elucidation by Robert Woodward, Lloyd Hillyard Conover, and others in the 1950s, tetracyclines have become preferred targets for natural product synthesis. However, on industrial scale, they became readily available by fermentation and partial synthesis. Their casual and thoughtless use in the initial decades after launch not only in humans but for veterinary purposes and as growth-enhancement agents in meat production rapidly led to the emergence of resistance. In an arms race for new antibiotics, more and more new drugs have been developed to deal with the threat. In this ongoing endeavor, a remarkable milestone was set by Andrew Myers in 2005 with the convergent total synthesis of (−)-doxycycline, as well as numerous azatetracyclines and pentacyclines, which has inspired chemists in the pharmaceutical industry to discover novel and highly active tetracyclines in recent years. Graphic abstract

Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis

“…These resistance mechanisms include (1) most commonly, efflux pumps, especially for first-generation tetracyclines, (2) ribosomal protection proteins (RPPs), which can block binding to tRNA even though tetracycline is already bound to the ribosome or cause detachment of the drug from its binding site, (3) enzymatic inactivation with NADPH-dependent oxidoreductase, and (4) reduced cell wall permeability. 103 , 104 …”

Navigating Antibacterial Frontiers: A Panoramic Exploration of Antibacterial Landscapes, Resistance Mechanisms, and Emerging Therapeutic Strategies

“…This class of antibiotics is effective against a wide range of Gram-positive and Gram-negative bacteria. Members of this family are effective against: Yersinia pestis , Vibrio cholera , Salmonella enterica , Treponema pallidum , Legionella pneumophila , Bacillus anthracis , Borrelia burgdoferi , Borrelia afzelii , Borrelia garinii , Borrelia recurrentis , Mycobacterium tuberculosis , Coxiella burnetii , Rickettsia ricketsii , Mycobacterium leprae , Mycobacterium marinum , Mycoplasma pneumoniae , S. aureus (including MRSA), Vibrio vulnificus , and vancomycin-resistant Enterococcus . , Their main mechanism of action is the inhibition of protein synthesis in bacteria. They bind reversibly to the A-site of the 30S ribosomal unit to interfere with the binding of the aminoacyl-tRNA to the acceptor site of the mRNA–ribosome complex, which prevents the addition of new amino acids to the growing peptides and impairs the cells’ ability to grow or replicate.…”

“…They bind reversibly to the A-site of the 30S ribosomal unit to interfere with the binding of the aminoacyl-tRNA to the acceptor site of the mRNA–ribosome complex, which prevents the addition of new amino acids to the growing peptides and impairs the cells’ ability to grow or replicate. Still, bacterial resistance has developed via reduction of intracellular concentration by active efflux, disruption of the interaction with the 30S subunit by ribosomal protective proteins (TetM and TetO), deactivation via hydroxylation of position C-11a (TetX and Tet 37), and mutation of the binding site . Recent literature has further discussion on resistance, synthesis, photoactivation, new applications, modifications, and the new generation of tetracyclines. − …”

Photocatalytic Degradation of Tetracycline Hydrochloride by Zinc oxide/Polypyrrole/Carbon nanotubes

“…Some are also used to treat malaria, Lyme disease, tuberculosis, Rocky Mountain spotted fever and leprosy. [10][11][12] Most antibiotics in the aquatic environment are caused by the direct use of drugs in aquaculture. Traditional sewage treatment methods still result in some residues in the water environment, which have not been fully absorbed and removed.…”