The Synthesis Of Isoxazoline Derivatives And Their Antibacterial Activity

The development of bacterial resistance to currently available antibacterial agents is a growing global health problem. Of particular concern are infections caused by multidrug-resistant Gram-positive pathogens. Principal players among these problematic organisms are isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), vancomycinresistant Enterococcus faecalis and Enterococcus faecium (VREF), and also penicillin and cephalosporin resistant Streptococcus pneumoniae. These pathogens are responsible for significant morbidity and mortality in both the hospital and community setting. A new and promising group of antibacterial agents, collectively known as the oxazolidinones and exemplified by linezolid (PNU-100766, marketed as Zyvox), have recently emerged as important new therapeutic agents for the treatment of infections caused by Gram positive bacteria. The oxazolidinone class of antibacterial agents selectively binds to the 23S RNA component of the 50S ribosomal subunit and prevents the formation of a functional 70S initiation complex, inhibiting protein synthesis at the early stage. Due to its unique mechanism of action, there are fewer cross-resistances between the oxazolidinones and other families of antibacterial agents. Previous literature on the structure-activity relationships for the oxazolidinones has demonstrated that the oxazolidinone ring and the isoxazoline ring are bioisosteres. Furthermore, the compounds carrying isoxazoline ring can be used for the protection of plant from diseases, and fungicidal against phytophthora infestation on tomatoes. About 45 compounds were synthesized according to the combination principles.The antibacterial activity of the new compounds has been tested. Fortunately, some of the compounds have novel antibacterial activity. Studies to establish their in vivo efficacy and safety are being planned for further development.