simocyclinone-d8 and Escherichia-coli-Infections

The increasing occurrence of drug-resistant bacterial infections in the clinic has created a need for new antibacterial agents. Natural products have historically been a rich source of both antibiotics and lead compounds for new antibacterial agents. The natural product simocyclinone D8 (SD8) has been reported to inhibit DNA gyrase, a validated antibacterial drug target, by a unique catalytic inhibition mechanism of action. In this work, we have prepared simplified flavone-based analogues inspired by the complex natural product and evaluated their inhibitory activity and mechanism of action. While two of these compounds do inhibit DNA gyrase, they do so by a different mechanism of action than SD8, namely DNA intercalation.

Topics: Anti-Bacterial Agents; Coumarins; DNA Gyrase; Escherichia coli; Escherichia coli Infections; Flavones; Glycosides; Humans; Models, Molecular; Topoisomerase II Inhibitors