Development of Natural Product Inspired Adjuvants to Treat Tolerant Infections

项目摘要 在过去的几十年里，天然产品一直是药物的生产来源， 代表了，或者是灵感，大多数抗菌化合物已经进入 诊所该提案的目标是开发基于海洋生物的新型抗菌佐剂 天然产物synoxazolidinone B用于治疗革兰氏阳性骨科关节感染。这些 支架具有清除生物膜相关的寄生虫感染的潜力， 体外数据。这些与生物膜有关的感染对传统抗生素具有耐受性， 由于高达80%的人类感染涉及生物膜相关的 微生物的很少有小分子被分离出来，有可能破坏 生物膜，从而起到清除生物膜相关感染的作用。在此，我们建议开发 一类能够治疗生物膜相关感染的化合物 并生成必要的关键数据，用于决定是否将这些分子推向 a II期临床前研究。

Project Summary Natural products have served as a productive source of drugs over the past decades and have represented, or been the inspiration for, a majority of antimicrobial compounds that have entered the clinic. The goal of this proposal is to develop novel antibacterial adjuvants based on the marine natural product synoxazolidinone B to treat Gram-positive orthopedic joint infections. These scaffolds have the potential to clear biofilm-implicated recalcitrant infections based on preliminary in-vitro data. These biofilm-implicated infections are tolerant to traditional antibiotics and represent a significant clinical need since up to 80% of human infections involve biofilm-associated microorganisms. Few small molecules have been isolated that have the potential to disrupt biofilms, thereby functioning to clear biofilm associated infections. Herein, we propose to develop a class of compounds that is capable to addressing the treatment of biofilm associated infections and generate the key data necessary for a go/no-go decision to advance these molecules toward a Phase II pre-clinical study.