Novel Compounds from Sycamore Leaves for the Treatment of MRSA

来自梧桐叶的新型化合物可用于治疗 MRSA

• 批准号: 8832837
• 负责人: Jiajiu Shaw
• 金额: $ 30.37万
• 依托单位: 21ST CENTURY THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2016-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8832837
• 关键词: Acute; Address; American; Animal Model; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Biological; Biological Availability; Bolus Infusion; Capital; Chronic; Clinical; Clinical Research; Communities; Conduct Clinical Trials; Data; Development; Drug Formulations; Drug Kinetics; Drug resistance; Economic Development; Erythromycin; Exhibits; Folk Medicine; Funding; Glycosides; Growth; Health; Health Care Costs; Healthcare; Hematopoietic System; Hospitals; Human; In Vitro; Individual; Industry; Infection; Injection of therapeutic agent; Kidney; Length of Stay; Liver; Maximum Tolerated Dose; Medical; Microbiological Techniques; Mus; Paper; Patients; Penicillins; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plant Leaves; Plants; Preparation; Procedures; Production; Property; Proteomics; Public Health; Quality Control; Resistance; Small Business Innovation Research Grant; Superbug; Technology; Tetracyclines; Therapeutic; Therapeutic Effect; Toxic effect; Treatment Efficacy; United States National Institutes of Health; Vancomycin; Vancomycin-resistant S. aureus; in vivo; kaempferol; meetings; methicillin resistant Staphylococcus aureus; mortality; novel; pathogen; phase 1 study; phase 2 study; pre-clinical; public health relevance; resistant strain; scale up; success

 DESCRIPTION (provided by applicant): Methicillin-resistant staphylococcus aureus (MRSA) is a serious pathogen that can cause patient mortality and extend hospital stays, resulting in higher health care costs. Currently, over 50% of staph cases around the world are caused by MRSA. In recent years, MRSA has evolved into several resistant strains that can resist to multiple antibiotics such as penicillin, vancomycin, tetracycline and erythromycin. For this reason, they are sometimes called "superbugs." In recent years, these "superbugs" have become a serious threat to public health. Because of the increasing presence of MRSA-related infections, especially in hospitals, there are urgent needs for effective and novel antibiotic therapies. In a preliminary study, we have isolated a novel compound, kaempferol 3-O-alpha-L-(2",3"-di-p-coumaroyl)rhamnoside (KCR) from the American sycamore (Platanus occidentalis) that were active against MRSA and VRSA (vancomycin resistant staphylococcus aureus) in vitro and in vivo. The sycamore materials have been classified by the USDA as generally regarded as safe (GRAS) because of extensive human contact and use of this plant in traditional folk medicines and paper industry, among others. Active metabolites of these anti-MRSA compounds likely possess a distinct mechanism of action as they do not show cross resistance or structural homology with established antibiotics. In this proposal, we plan to furthe investigate these highly selective anti-MRSA KCR (platanosides) including the maximum tolerated dose (MTD), therapeutic efficacy, pharmacokinetics (PK), mechanism of action, and in vivo toxicity using animal model and microbiological techniques. This project clearly has the potential to generate a first in class new antibiotic with a novel mechanism of action and provides a unique opportunity for US economic development. In addition, the success of this project will address the limitations of current therapies for the control of MRSA and other antibiotic-resistant staph infections such as VRSA.