UC San Diego

Growing antibiotics resistance and the limited amount of effective antibiotics against Gram-negative pathogens are the most alarming problems in clinic; therefore, the search for new board-spectrum antibacterial agents becomes an imminent task in the pharmaceutical industry. Researches have shown that Tricyclic Gyrase (GyrB/ParE) Inhibitors are a new class of board-spectrum antibacterial agents which are effective against multi-drug resistant bacteria strains. Pharmaceutical companies like Trius had synthesized such inhibitors but none of the inhibitors has made into clinical trials yet due to various safety issues and solubility problems. In this research, new tricyclic gyrase inhibitors were synthesized by modifying the functional groups. Minimum Inhibitory Concentration (MIC) Assays were used to examine their board-spectrum antibacterial potencies against nine total bacteria strains, including multi-drug resistant strains. The results showed that two of the synthesized compounds, D18 and Tri-1, have board-spectrum antibacterial activities and works against multi-drug resistant strains. Compounds Tri-2, Tri-3, and Tri-4 showed activity against Gram-positive bacteria only while compound Tri-5 showed poor antibacterial activity possible due to the 2-Methylpyrimmdin.