Semisynthetic derivatives of mannopeptimycin antibiotics active against multi-drug resistant Gram-positive bacteria

Abstract

The incidence of hospital infections due to Gram-positive bacteria is continuously increasing. Most of these organisms have become resistant to first-line antibacterial agents and they pose a serious clinical problem as current therapeutic options are limited. It follows an urgent need for new agents, possibly provided with novel mechanisms of action, that prove to be effective against multi-drug resistant Gram-positive pathogens, particularly methicillin-resistant staphylococci, including strains of Staphylococcus aureus with reduced susceptibility to glycopeptides, penicillin-resistant pneumococci and vancomycin-resistant enterococci. In this patent, American Cyanamide Co. presents a new class of glycopeptide derivatives of the natural products mannopeptimycins, which do not belong to the vancomycin family, that show interesting activity against most of the above resistant Gram-positive bacteria. Some of these compounds are worthy of further development to be considered as a possible alternative to other innovative antibiotics that have been launched into the market recently or are currently undergoing clinical development.

• antibacterial agents
• cyclic glycopeptides
• methicillin-resistant Staphylococcus aureus(MRSA)
• penicillin-resistant (Pen-R) pneumococci
• resistant Gram-positive infections
• vancomycin-resistant enterococci (VRE).