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Chemical Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with Substituted Amino Moiety.doc

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Chemical Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with Substituted Amino Moiety

ChemicalSynthesisandBiologicalActivitiesofNovel PleuromutilinDerivativeswithSubstitutedAmino Moiety RuofengShang1,ShengyuWang2,XimingXu3,YunpengYi1,WenzhuGuo1, YuLiu1,JianpingLiang1* 1KeyLaboratoryofNewAnimalDrugProjectofGansuProvince,KeyLaboratoryofVeterinaryPharmacceuticalDevelopment,MinistryofAgriculture,LanzhouInstituteof Animal Science and Veterinary Pharmaceutics Science, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China, 2University Hospital of Gansu Traditional ChineseMedicine,Lanzhou,Gansu,China,3Universite′ ParisDiderot,SorbonneParisCite′,Unite′ deBiologieFonctionnelleetAdaptative,CNRS,Paris,France Abstract Novelpleuromutilinderivativesdesignedbasedonthestructureofvalnemulinweresynthesizedandevaluatedfortheirin vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcusagalactiae.Compound5bshowedthehighestantibacterialactivitiesandevenexceededtiamulin.Moreover, thedockingexperimentsprovidedinformationaboutthebindingmodelbetweenthesynthesizedcompoundsandpeptidyl transferasecenter(PTC)of23SrRNA. Citation:ShangR,WangS,XuX,YiY,GuoW,etal.(2013)ChemicalSynthesisandBiologicalActivitiesofNovelPleuromutilinDerivativeswithSubstitutedAmino Moiety.PLoSONE8(12):e82595.doi:10.1371/journal.pone.0082595 Editor:PatrickM.Schlievert,UniversityofIowaCarverCollegeofMedicine,UnitedStatesofAmerica ReceivedAugust13,2013;AcceptedOctober25,2013;PublishedDecember23,2013 Copyright: ? 2013 Shang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyBasicScientificResearchFundsinCentralAgricultralScientificResearchInstitutions(number1610322013004)and‘‘Five- Y