Synthesis and Evaluation of Troponoids as a New Class of Antibiotics.

Novel antibiotics are urgently needed. The troponoids [tropones, tropolones, and α-hydroxytropolones (α-HT)] can have anti-bacterial activity. We synthesized or purchased 92 troponoids and evaluated their antibacterial activities against , , and . Preliminary hits were assessed for minimum inhibitory concentrations (MIC) and cytotoxicity (CC) against human hepatoma cells. Sixteen troponoids inhibited // growth by ≥80% growth at <30 μM with CC values >50 μM. Two selected tropolones ( and ) inhibited 18 methicillin-resistant (MRSA) strains with similar MIC values as against a reference strain. Two selected thiotropolones ( and ) inhibited multidrug-resistant (MDR) with MIC ≤30 μM. One α-HT () inhibited MDR- with MIC ≤30 μM. This study opens new avenues for development of novel troponoid antibiotics to address the critical need to combat MDR bacterial infections.