tigecycline and Pseudomonas-Infections

Utilizing a total synthesis approach, the first 8-heterocyclyltetracyclines were designed, synthesized, and evaluated against panels of tetracycline- and multidrug-resistant Gram-positive and Gram-negative pathogens. Several compounds with balanced, highly potent in vitro activity against a broad range of bacterial isolates were identified through structure-activity relationships (SAR) studies. One compound demonstrated the best antibacterial activity against Pseudomonas aeruginosa both in vitro and in vivo for tetracyclines reported to date.

Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Halogenation; Humans; Pseudomonas aeruginosa; Pseudomonas Infections; Pyrrolidinones; Tetracycline Resistance; Tetracyclines

A series of novel hexacyclic tetracycline analogues ("hexacyclines") was designed, synthesized, and evaluated for antibacterial activity against a wide range of clinically important bacteria isolates, including multidrug-resistant, Gram-negative pathogens. Valuable structure-activity relationships were identified, and several hexacyclines displayed potent, broad spectrum antibacterial activity, including promising anti-Pseudomonas aeruginosa activity in vitro and in vivo.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Drug Design; Female; Humans; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Pseudomonas aeruginosa; Pseudomonas Infections; Structure-Activity Relationship; Tetracyclines; Thigh