Novel Compounds from Sycamore Leaves for the Treatment of MRSA
Novel Compounds from Sycamore Leaves for the Treatment of MRSA
批准号:
8832837
负责人:
Jiajiu Shaw
金额:
$30.37万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-08-15 至 2016-09-15
关键词:
AcuteAddressAmericanAnimal ModelAntibiotic ResistanceAntibiotic TherapyAntibioticsBiologicalBiological AvailabilityBolus InfusionCapitalChronicClinicalClinical ResearchCommunitiesConduct Clinical TrialsDataDevelopmentDrug FormulationsDrug KineticsDrug resistanceEconomic DevelopmentErythromycinExhibitsFolk MedicineFundingGlycosidesGrowthHealthHealth Care CostsHealthcareHematopoietic SystemHospitalsHumanIn VitroIndividualIndustryInfectionInjection of therapeutic agentKidneyLength of StayLiverMaximum Tolerated DoseMedicalMicrobiological TechniquesMusPaperPatientsPenicillinsPharmaceutical PreparationsPharmacologic SubstancePhasePlant LeavesPlantsPreparationProceduresProductionPropertyProteomicsPublic HealthQuality ControlResistanceSmall Business Innovation Research GrantSuperbugTechnologyTetracyclinesTherapeuticTherapeutic EffectToxic effectTreatment EfficacyUnited States National Institutes of HealthVancomycinVancomycin-resistant S. aureusin vivokaempferolmeetingsmethicillin resistant Staphylococcus aureusmortalitynovelpathogenphase 1 studyphase 2 studypre-clinicalpublic health relevanceresistant strainscale upsuccess
中文摘要
英文摘要
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.
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