Anthranilic Acid Derivatives as Novel Antibiotics against MRSA and other Gram Positive Microorganisms: Combating Antibiotic Resistance

Abstract

Implementation of antibiotics to treat bacterial infections began during World War II. Since then, a number of antibiotic resistance microorganisms have emerged, one of these being Methicillin Resistant Staphylococcus aureus (MRSA). This resistance can be accredited to multiple factors, but the greatest contributors are the similarity in the chemical composition of the commonly prescribed antibiotics used to treat MRSA and the improper use and disposal of these agents. MRSA is the most frequent health acquired infection in the United States and to combat this growing problem, we have developed a novel class of antibiotics derived from anthranilic acids that show antibacterial activity against MRSA. Our derivatives record a minimum inhibitory concentration (MIC) ranging from 2-64 μg/ml, however when in the presence of human serum protein (HSP) this value increases, decreasing their effectiveness. We have identified a component of HSP, albumin, that causes the increase in MIC, and have determined that intermolecular hydrogen bonding is the cause of this increase. Using this information we are currently synthesizing new derivatives with a low binding affinity for albumin, or when bound do not lose antibacterial activity