A Novel Approach to Antibiotic and Anti-biofouling Activities of Natural Phenols

天然酚类抗生素和抗生物污垢活性的新方法

• 批准号: 0626022
• 负责人: Dong-Shik Kim
• 金额: --
• 依托单位: University of Toledo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0626022&HistoricalAwards=false
• 关键词: Novel; Approach; Antibiotic; Anti; biofouling

ABSTRACTPI: Dong-Shik Kim and Xuefei Huang Institution: University of ToledoProposal Number: 0626022Title: A Novel Approach to Antibiotic and Anti-biofouling Activities of Natural PhenolsProject SummaryNatural phenolic compounds are known for unique antibiotic and antioxidant activities that can be used for medical, pharmaceutical, and industrial applications. In this research, several natural phenolic compounds will be selected as model compounds, and will be polymerized and crosslinked to form permanent antibiotic and anti-biofouling coatings. The structure-activity relationships will be investigated, and novel antibiotic anti-biofouling mechanisms will be suggested. The redox potential (i.e., antioxidant activity) of these compounds will be used to delineate possible new anti-biofouling mechanisms.Preliminary experiments show unique antibiotic and anti-biofouling activities of the model compounds and their polymers and coatings. These activities are thought to be possible by a combinatory effect of strong redox potential and hydrogen bonding between the cell membranes and phenolic compounds as well as the long alkyl chains membrane penetrating effect. The redox potential is controlled by the phenol ring substituents such as OH and COOH, and ester-linkage, and it is thought that the electron transport system (ETS) and cellular membrane enzymes are disturbed by redox potential, which leads to cell death. For the anti-biofouling activity of the coating, the interaction between the phenolic compound and exopolymer-inducing sensing molecules of the microbes, e.g., acyl-homoserine lactone (AHL), will be investigated to verify the novel anti-biofouling mechanisms. Various structures of the model compounds will be separated, synthesized, polymerized and characterized to determine the structure-activity relationship. The enzymatically synthesized polymers will also be used to form polymers with well-defined structures and permanent anti-biofouling coating on the solid surface.Intellectual Merit1) The suggested antibiotic mechanisms are thought to be different from those of existing antibiotics, and expected to contribute to development of new antibiotics that reduce antibiotic resistance. 2) The suggested mechanisms of deactivation of quorum sensing molecules and membrane enzymes by hydroxyl radicals are a novel approach that will provide a better understanding on anti-biofouling mechanisms and strategies. 3) Enzymatic polymerization of the renewable resources is a precise and environmentally benign process that dovetails with synthesis of new materials from renewable resources. 3) Measuring redox potential of the coating using a gold interdigitated electrode film and impedance analyzer will be used (it is also considered a valuable tool for easy and accurate measurement of anti- or prooxidant activity of solid materials).Broader Impacts1) Undergraduate students and local high school students from underrepresented areas will participate in the project in order to integrate research activities into the teaching of science and engineering at broader levels. 2) The anti-biofouling coatings developed in this study are efficient and environmentally-benign, and expected to make significant impacts on ships, catheters, food processors, medical/dental devices, and water distribution systems. 4) Measurement of the redox potential of solid coating by using an interdigitated electrode film and ac impedance analyzer can be applied to ultra-sensitive biochemical sensors for detecting low concentrations of free radicals in environmental pollutants or in the early stage of carcinogenesis or tumorigenesis.

摘要：Dong-Shik Kim和Xuefei Huang机构：托莱多大学提案编号：0626022标题：天然酚类化合物的抗生素和抗生物污损活性的新方法项目概述天然酚类化合物因其独特的抗生素和抗氧化活性而闻名，可用于医疗，制药和工业应用。本研究以几种天然酚类化合物为模型化合物，将其聚合交联，制备出永久性抗菌抗生物污损涂料。将研究结构-活性关系，并提出新的抗生素抗生物污损机制。氧化还原电位（即，抗氧化活性）来描述可能的新的抗生物污损机理。初步实验显示了模型化合物及其聚合物和涂层独特的抗菌和抗生物污损活性。这些活动被认为是可能的组合效应的强氧化还原电位和细胞膜和酚类化合物之间的氢键，以及长烷基链的膜渗透效果。氧化还原电位受酚环取代基（如OH和COOH）和酯键控制，并且认为氧化还原电位干扰电子传递系统（ETS）和细胞膜酶，导致细胞死亡。对于涂层的抗生物污染活性，酚类化合物与微生物的外聚合物诱导传感分子之间的相互作用，酰基高丝氨酸内酯（阿勒），将被研究，以验证新的抗生物污损机制。将对模型化合物的各种结构进行分离、合成、聚合和表征，以确定结构-活性关系。酶促合成的聚合物也将用于形成具有明确结构的聚合物，并在固体表面上形成永久的抗生物污损涂层。知识价值1）所提出的抗生素机制被认为与现有抗生素的机制不同，并有望有助于开发新的抗生素，减少抗生素耐药性。2)提出的羟基自由基对群体感应分子和膜酶的失活机制是一种新的方法，将为更好地理解抗生物污损的机制和策略提供帮助。3)可再生资源的酶促聚合是一种精确且环境友好的过程，其与从可再生资源合成新材料密切相关。3)将使用金叉指电极膜和阻抗分析仪测量涂层的氧化还原电位（它也被认为是一种简单而准确地测量固体材料的抗氧化或促氧化活性的宝贵工具）。来自代表性不足地区的本科生和当地高中生将参加该项目，以便将研究活动融入科学和在更广泛的层面上进行工程设计。2)本研究中开发的抗生物污损涂料是有效的，对环境友好的，预计将对船舶，导管，食品加工机，医疗/牙科设备和配水系统产生重大影响。4)用叉指电极膜和交流阻抗分析仪测量固体涂层的氧化还原电位，可应用于超灵敏生化传感器，用于检测环境污染物中的低浓度自由基或癌变或肿瘤发生的早期阶段。