Identification and characterization of a new antimicrobial chemical series

新型抗菌化学品系列的鉴定和表征

• 批准号: 533399-2018
• 负责人: Forgione, Pat
• 金额: $ 1.82万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=650943
• 关键词: Identification; characterization; new; antimicrobial; chemical

Antibiotic resistance represents a major health problem for society. With the expanded use of antibiotics,**microorganisms have developed various mechanisms of resistance to overcome the cytotoxic effects of once**highly effective agents. Staphylococcus aureus (S. aureus) represents one such organism that has developed**rapid resistance to methicillin two years after its introduction into clinical settings. However,**methicillin-resistant S. aureus (MRSA) has started to show resistance to vancomycin, considered the standard**of care for the last decades. There is therefore an urgent need to identify novel therapeutics to counteract**resistant strains. The proposed project aims at identifying new chemical series that can overcome the antibiotic**resistance observed with Enterococci and MRSA. Starting from an initial proprietary compound, the physical**and chemical properties of the series will be investigated and enhanced to ensure high potency with good**solubility and pharmacokinetic properties. Structure activity relationship (SAR) studies will be performed**using in vitro assays and assess the minimal inhibitory concentration (MIC) and bactericidal activity of each**chemical series.

抗生素耐药性是一个重大的社会健康问题。随着抗生素应用的扩大，微生物已经发展出多种耐药机制，以克服曾经高效的药物的细胞毒性作用。金黄色葡萄球菌(S.金黄色葡萄球菌）代表了一种这样的生物体，其在甲氧西林被引入临床环境中两年后已经发展出对甲氧西林的快速耐药性。然而，** 耐甲氧西林S。金黄色葡萄球菌（MRSA）已经开始表现出对万古霉素的耐药性，万古霉素被认为是过去几十年的标准治疗。因此，迫切需要鉴定新的治疗剂来对抗 ** 抗性菌株。拟议项目旨在确定可克服肠球菌和MRSA的抗生素 ** 耐药性的新化学品系列。从最初的专利化合物开始，将研究并增强该系列的物理 ** 和化学性质，以确保具有良好 ** 溶解度和药代动力学性质的高效价。将使用体外试验进行 ** 构效关系（SAR）研究，并评估每个 ** 化学品系列的最低抑菌浓度（MIC）和杀菌活性。