NOVEL MARINE ANTIMICROBIAL LIPIDS

新型海洋抗菌脂质

• 批准号: 6472792
• 负责人: Nestor Manuel Carballeira
• 金额: $ 11.03万
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6472792
• 关键词: Dinoflagellates; Porifera; Staphylococcus; Streptococcus; antibacterial agents; aquatic organism; bioassay; chemical structure function; drug design /synthesis /production; drug discovery /isolation; fatty acid analog; gram positive bacteria; lipid structure; pharmacokinetics

Description (Adapted from Application): This proposal aims at the discovery of new marine lipids (either natural or synthetic) with potential applications as novel antimicrobial agents. The study of unusual and characteristic fatty acid profiles of marine microorganisms, some implicated in ciguatera food poisoning, is also contemplated in this research program. The long-range investigation is directed towards: 1) the discovery of new marine lipids (either natural or synthetic) with sufficient antimicrobial activity against pathogenic gram-positive bacteria (gram-negative bacteria will also occasionally be tested) so as to permit their utilization as antibacterial drugs or synergistically with known antibiotics, and 2) the synthesis of new synthetic fatty acid analogs, as well as alkylglycerol derivatives, with considerable antimicrobial activity against pathogenic antibiotic-resistant staphylococci and streptococci. In particular, the investigator proposes to expand the search for novel fatty acids to a series of tropical marine organisms (such as sponges rich in symbiotic cyanobacteria, marine bacteria, and toxic dinoflagellates) in search of previously unidentified fatty acids and/or novel structural motifs. The new fatty acids (and their analogs) will be synthesized, which will provide sufficient quantities for antimicrobial bioassays. In addition, alkylglycerol derivatives of the most promising antimicrobial fatty acids will also be synthesized since, in some cases, these derivatives tend to display stronger antimicrobial activity than the parent fatty acids. The new lipids will be primarily scrutinized for their antimicrobial activity against gram-positive bacteria (as suggested by preliminary results), such as pathogenic staphylococci and streptococci. They will put a special emphasis in the toxicity of these lipids against the cariogenic bacterium Streptococcus mutans, a primary cause of dental caries. The most active alkylglycerols and/or fatty acids will be further tested against known antibiotic-resistant bacteria, such as vancomycin resistant streptococci, chosen on the basis of their availability.

描述（改编自应用）：本提案旨在发现 新的海洋脂质（天然或合成），具有潜在的应用， 新型抗菌剂。特殊脂肪酸的研究 海洋微生物概况，其中一些与雪卡毒食物中毒有关， 也在这个研究计划中。长期调查是 目的是：1）发现新的海洋脂质（天然或 合成）具有足够的抗病原体的抗微生物活性 革兰氏阳性菌（革兰氏阴性菌偶尔也会 测试），以允许它们用作抗菌药物，或 与已知抗生素协同作用，和2）合成新的合成 脂肪酸类似物，以及烷基甘油衍生物，具有相当大的 抗病原性耐药性葡萄球菌的抗菌活性 和链球菌。 特别是，研究人员建议扩大对新脂肪酸的研究， 酸对一系列热带海洋生物（例如富含维生素C的海绵）的影响 共生蓝藻、海洋细菌和有毒甲藻） 以前未鉴定的脂肪酸和/或新的结构基序。新 脂肪酸（及其类似物）将被合成，这将提供 足够量用于抗微生物生物测定。此外，烷基甘油 最有前途的抗微生物脂肪酸的衍生物也将 合成，因为在某些情况下，这些衍生物往往表现出更强的 抗微生物活性高于母体脂肪酸。新的脂质将 主要针对其对革兰氏阳性菌的抗菌活性进行审查， 细菌（如初步结果所示），如致病性 葡萄球菌和链球菌。他们将特别强调 这些脂质对致龋细菌变形链球菌的毒性， 龋齿的主要原因。最具活性的烷基甘油和/或脂肪酸 酸将进一步测试对已知的耐药性细菌，如 作为万古霉素抗性链球菌，基于其 空房的