The glycylcyclines: a comparative review with the tetracyclines (original) (raw)
Related papers
Journal of Medicinal Chemistry, 1994
This report describes the discovery of a new generation of tetracycline antibacterial agents, the "glycylcyclines". These agents are notable for their activity against a broad spectrum of tetracyclinesusceptible and-resistant Gram-negative and Gram-positive aerobic and anaerobic bacteria possessing various classes of tetracycline-resistant determinants [ tet B (efflux), tet M (ribosomal protection)]. The design and synthesis of a number of 7-substituted 9-substituted-amido 6-demethyl-6-deoxytetracyclines are described.
The Development of Third-Generation Tetracycline Antibiotics and New Perspectives
Pharmaceutics, 2021
The tetracycline antibiotic class has acquired new valuable members due to the optimisation of the chemical structure. The first modern tetracycline introduced into therapy was tigecycline, followed by omadacycline, eravacycline, and sarecycline (the third generation). Structural and physicochemical key elements which led to the discovery of modern tetracyclines are approached. Thus, several chemical subgroups are distinguished, such as glycylcyclines, aminomethylcyclines, and fluorocyclines, which have excellent development potential. The antibacterial spectrum comprises several resistant bacteria, including those resistant to old tetracyclines. Sarecycline, a narrow-spectrum tetracycline, is notable for being very effective against Cutinebacterium acnes. The mechanism of antibacterial action from the perspective of the new compound is approached. Several severe bacterial infections are treated with tigecycline, omadacycline, and eravacycline (with parenteral or oral formulations)....
American Journal of Physiology-Cell Physiology, 2010
There must be something unique about a class of drugs (discovered and developed in the mid-1940s) where there are more than 130 ongoing clinical trials currently listed. Tetracyclines were developed as a result of the screening of soil samples for antibiotic organisms. The first of these compounds chlortetracycline was introduced in 1948. Soon after their development tetracyclines were found to be highly effective against various pathogens including rickettsiae, Gram-positive, and Gram-negative bacteria, thus, becoming a class of broad-spectrum antibiotics. The mechanism of action of tetracyclines is thought to be related to the inhibition of protein synthesis by binding to the 30S bacterial ribosome. Tetracyclines are also an effective anti-malarial drug. Over time, many other “protective” actions have been described for tetracyclines. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Its mechanism of action appears to relate to spec...
Brazilian Journal of Infectious Diseases, 2005
The in vitro activity of tigecycline (former GAR-936), a new semisynthetic tetracycline, was evaluated in comparison with tetracycline and other antimicrobial agents. Material and Methods: A total of 1,326 contemporary clinical isolates collected from the Latin American region were collected in 2000-2002 period and tested with microdilution broth according to the CLSI guidelines. The bacterial pathogens evaluated included Staphylococcus aureus (505), Streptococcus pneumoniae (269), coagulase-negative staphylococci (CoNS; 227), Haemophilus influenzae (129), Enterococcus spp. (80), Moraxella catarrhalis (54), β β β β β-haemolytic streptococci (28), viridans group streptococci (26), and Neisseria meningitidis (8) Results: Tigecycline demonstrated excellent activity against all Gram-positive cocci, with 90% of penicillin-resistant S. pneumoniae strains being inhibited at 0.12 µ µ µ µ µg/mL, while the same isolates had an MIC 90 of > 16 µ µ µ µ µg/mL for tetracycline. All Enterococcus spp. were inhibited at 0.25 µ µ µ µ µg/mL of tigecycline. Tigecycline (MIC 50 , 0.25 µ µ µ µ µg/mL) was eight-fold more potent than minocycline (MIC 50 , 2 µ µ µ µ µg/mL) against oxacillin-resistant S. aureus (ORSA); all ORSA were inhibited at ≤ ≤ ≤ ≤ ≤ 2 µ µ µ µ µg/mL of tigecycline. Tigecycline demonstrated excellent activity (MIC 50 , 0.5 µ µ µ µ µg/mL) against CoNS with reduced susceptibility to teicoplanin (MIC, 16 µ µ µ µ µg/mL). Tigecycline also showed high potency against respiratory pathogens such as M. catarrhalis (MIC 50 , 0.12 µ µ µ µ µg/mL) and H. influenzae (MIC 50 , 0.5 µ µ µ µ µg/mL). No tigecycline resistant isolates were detected when the proposed susceptible breakpoints (≤ ≤ ≤ ≤ ≤ 4 µ µ µ µ µg/mL) was applied. Conclusions: This results indicate that tigecycline has potent in vitro activity against clinically important pathogenic bacteria, including Gram-positive isolates resistant to both tetracycline and minocycline.
Diagnostic Microbiology and Infectious Disease, 2000
The in vitro activity of GAR-936, a new semisynthetic glycylcycline, was evaluated in comparison with two tetracyclines and several other antimicrobial agents. A total of 1, 203 recent clinical isolates were tested by reference broth or agar dilution methods. Among the members of the family Enterobacteriaceae, GAR-936 was generally two-to four-fold more active than minocycline, and two-to 16-fold more active than tetracycline. All enteric bacilli MIC 90 results were Յ 4 g/mL; the exception being Proteus mirabilis and indole-positive Proteae (Ն 8 g/mL). GAR-936 demonstrated excellent activity against all Gram-positive cocci with 90% of the penicillin-resistant Streptococcus pneumoniae isolates inhibited at 0.03 g/ml, while the same isolates had a MIC 90 of 8 and Ͼ 8 g/mL for minocycline and tetracycline, respectively. All Enterococcus spp., including vancomycin-resistant isolates, were inhibited at 0.25 g/mL of GAR-936 (MIC 90 , 0.12 or 0.25 g/mL). Although GAR-936 (MIC 50 , 0.25 g/mL) was two-fold less active than minocycline (MIC 50 , 0.12 g/mL) against oxacillin-resistant Staphylococcus aureus, all isolates were inhibited at Յ 0.25 g/mL. GAR-936 demonstrated good activity against nonfermentative bacteria such as Acinetobacter spp. (MIC 90 , 2 g/ml) and Stenotrophomonas maltophilia (MIC 90 , 4 g/mL), but the compound exhibited only modest activity against Pseudomonas aeruginosa (MIC 50 , 8 g/mL). Haemophilus influenzae (MIC 90 , 1-2 g/mL), Moraxella catarrhalis (MIC 90 , 0.12 g/mL), and various Neisseria spp. (MIC 90 , 0.12-0.5 g/mL) were susceptible to GAR-936. These results indicate that GAR-936 has potent in vitro activity against a wide range of clinically important pathogenic bacteria, and that several Gram-positive and -negative isolates resistant to older tetracyclines and other drug classes remain susceptible to GAR-936, the newest glycylcycline candidate for clinical use.
Review: Anti-infectives Advances in tetracycline antibiotics
Expert Opinion on Therapeutic Patents, 1995
The patent status of tetracycline research for the period of 1991 to 1995 is presented. Topics covered include new tetracyclines with intrinsic antibacterial activity against tetracycline-resistant bacteria or which potentiate the activity of the older tetracyclines, new natural products, new chemical methods, and non-infectious disease uses for tetracyclines.