NOVEL MARINE ANTIMICROBIAL LIPIDS

新型海洋抗菌脂质

• 批准号: 6358592
• 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: 1988
• 资助国家: 美国
• 起止时间: 1988-06-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6358592
• 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（根据应用程序改编）：该提案旨在发现 具有潜在应用的新型海洋脂质（天然或合成） 新型抗菌剂。不寻常和特征性脂肪酸的研究 海洋微生物的特征，有些与雪茄食品中毒有关 该研究计划也考虑了。远程调查是 针对：1）发现新的海洋脂质（自然或 合成）具有足够的抗菌活性对病原体的抗菌活性 革兰氏阳性细菌（革兰氏阴性细菌偶尔也会是 测试）以允许其用作抗菌药物或 与已知抗生素协同作用，以及2）新合成的合成 脂肪酸类似物以及烷基甘油衍生物，具有相当大的 针对病原性抗生素抗生素葡萄球菌的抗菌活性 和链球菌。 特别是，调查人员建议扩大寻找新型脂肪的搜索 酸到一系列热带海洋生物（例如富含海绵的海绵 搜索中的共生蓝细菌，海洋细菌和有毒的鞭毛鞭毛盐） 以前未鉴定的脂肪酸和/或新型结构基序。新的 将合成脂肪酸（及其类似物），这将提供 足够的抗菌生物测定。另外，烷基甘油 最有希望的抗菌脂肪酸的衍生物也将是 合成以来，在某些情况下，这些衍生物倾向于显示更强 抗菌活性比母脂肪酸。新脂质将是 主要审查其抗菌活性针对革兰氏阳性的活性 细菌（如初步结果所建议），例如致病性 葡萄球菌和链球菌。他们将特别重点 这些脂质对链球菌链球菌突变的毒性， 龋齿的主要原因。最活跃的烷基甘油和/或脂肪 酸将进一步测试已知的抗生素耐药菌，这样 作为万古霉素抗性链球菌，根据其选择 可用性。