An Artemisinin-Derived Dimer Has Highly Potent Anti-Cytomegalovirus (CMV) and Anti-Cancer Activities 英文参考文献.docVIP

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An Artemisinin-Derived Dimer Has Highly Potent Anti-Cytomegalovirus (CMV) and Anti-Cancer Activities 英文参考文献.doc

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An Artemisinin-Derived Dimer Has Highly Potent Anti-Cytomegalovirus (CMV) and Anti-Cancer Activities 英文参考文献

AnArtemisinin-DerivedDimerHasHighlyPotentAnti- Cytomegalovirus(CMV)andAnti-CancerActivities RanHe1,BryanT.Mott2,AndrewS.Rosenthal2,DouglasT.Genna2,GaryH.Posner2,3,RavitArav-Boger1* 1DepartmentofPediatrics,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica,2DepartmentofChemistry,SchoolofArtsand Sciences,TheJohnsHopkinsUniversity,Baltimore,Maryland,UnitedStatesofAmerica,3MalariaResearchInstitute,BloombergSchoolofPublicHealth,JohnsHopkins UniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica Abstract Werecentlyreportedthattwoartemisinin-deriveddimers(dimerprimaryalcohol606anddimersulfone4-carbamate832-4) aresignificantlymorepotentininhibitinghumancytomegalovirus(CMV)replicationthanartemisinin-derivedmonomers.In our continued evaluation of the activities of artemisinins in CMV inhibition, twelve artemisinin-derived dimers and five artemisinin-derived monomers were used. Dimers as a group were found to be potent inhibitors of CMV replication. ComparisonofCMVinhibitionandtheslopeparameterofdimersandmonomerssuggestthatdimersaredistinctintheir anti-CMV activities. A deoxy dimer (574), lacking the endoperoxide bridge, did not have any effect on CMV replication, suggestingarole fortheendoperoxidebridgeinCMVinhibition.Differencesinanti-CMVactivitywereobservedamong threestructuralanalogsofdimersulfone4-carbamate832-4indicatingthattheexactplacementandoxidationstateofthe sulfuratommaycontributetoitsanti-CMVactivity.Ofalltesteddimers,artemisinin-deriveddiphenylphosphatedimer838 provedtobethemostpotentinhibitorofCMVreplication,withaselectivityindexofapproximately1500,comparedtoour previouslyreporteddimersulfone4-carbamate832-4withaselectivityindexofabout900.Diphenylphosphatedimer838 washighlyactiveagainstaGanciclovir-resistantCMVstrainandwasalsothemostactivedimerininhibitionofcancercell growth.Thus,diphenylphosphatedimer838mayrepresentaleadfordevelopmentofahighlypotentandsafeanti-CMV compound. Citation:HeR,MottBT,RosenthalAS,GennaDT,Posne