Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Biotech 1, 800 East Leigh Street, Richmond, VA 23298, USA.
Bioorg Med Chem Lett. 2013 Nov 1;23(21):5874-7. doi: 10.1016/j.bmcl.2013.08.094. Epub 2013 Sep 5.
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.
临床上耐药菌感染的日益增多，使得人们需要开发新的抗菌药物。天然产物一直是抗生素和新型抗菌药物先导化合物的重要来源。天然产物西蒙环菌素 D8（SD8）通过一种独特的催化抑制作用机制，被报道能够抑制拓扑异构酶 II，这是一种经过验证的抗菌药物靶点。在这项工作中，我们受复杂天然产物的启发，制备了简化的黄酮类类似物，并评估了它们的抑制活性和作用机制。虽然其中两种化合物确实能抑制拓扑异构酶 II，但它们的作用机制与 SD8 不同，即 DNA 嵌入。
