Flavone-based analogues inspired by the natural product simocyclinone D8 as DNA gyrase inhibitors |
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| Authors: | Jenson Verghese Thuy Nguyen Lisa M Oppegard Lauren M Seivert Hiroshi Hiasa Keith C Ellis |
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| Institution: | 1. Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Biotech 1, 800 East Leigh Street, Richmond, VA 23298, USA;2. Department of Pharmacology, University of Minnesota Medical School, Nils Hasselmo Hall, 312 Church Street, Minneapolis, MN 55455, USA |
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| Abstract: | 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. |
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| Keywords: | Simocyclinone D8 DNA gyrase Antibiotics Natural product Flavone Quercetin |
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