选择性雌激素受体调节剂的分子对接和定量构效关系分析-molecular docking and quantitative structure-activity relationship analysis of selective estrogen receptor modulators.docxVIP

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选择性雌激素受体调节剂的分子对接和定量构效关系分析-molecular docking and quantitative structure-activity relationship analysis of selective estrogen receptor modulators.docx

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选择性雌激素受体调节剂的分子对接和定量构效关系分析-molecular docking and quantitative structure-activity relationship analysis of selective estrogen receptor modulators

重庆大学硕士学位论文substituentofBringandGlu305.TheresultsalsoshowthatitisfavorabletotheERβbindingaffinitieswhenDandEringinteractewiththehydrophobicresiduesIle373,Phe377andGly472,whichcontributetotheERβselectivespecificity.Basedonthedockingconformation,CoMFAandCoMSIAmodelswereestablished.ThebestmodeofERαistheCoMSIAmodelestablishedbythehydrophobicfield,andther2,q2(LOO)andr2edare0.977,0.583and0.508,prrespectively.ThebestCoMSIAmodelofERβisestablishedbyelectrostaticfield(12.0%)andhydrogenbonddonorfield(41.6%),andther2,q2(LOO)andr2edare0.778,0.508,and0.593,prrespectively.③Salicylaldximesderivatives:moleculardockingresultsshowthatthemaininteractionsbetweenligandandERαorERβarehydrogen-bondandhydrophobicinteractions.HydrophilicinteractionsbetweenligandsandresiduesGlu353andArg394causesasharpdecreaseinERαactivities.AndthestericeffectsbetweenR4substituentandhydrophobicresiduesIle376,Gly472,Leu476andLeu477arealsounfavorabletoERβactivities.Besides,electrostaticfieldcontributionstothemodelsmayplayamoreimportantroleinERβthanthatinERα.Basedonthedockingconformations,CoMFAandCoMSIAmodelsareestablished.ThebestERαmodeistheCoMSIAmodelestablishedbytheelectrostaticfield(39%)andhydrogen-bonddonor(61%),andther2,q2(LOO)andr2edare0.932,0.666,and0.589,prrespectively.ThebestERβCoMSIAmodelisestablishedbystericfield(29.5%)and(LOO)electrostaticfield(70.5%),ofwhichther2,q2andr2predare0.904,0.503,and0.944,respectively.④Pyrimidinesandpyrazinesderivatives:moleculardockingresultsshowedthatthethemaininteractionsbetweenligandandERαorERβwerehydrogenbondsandhydrophobicinteractions.ItisbenefittoincreaseVanderWaalsforceoftheposition6toincreaseERαbindingactivity.Basedonthedockingconformation,CoMFAandCoMSIAmodelswereestablished.ThebestERαmodeistheCoMSIAmodel,whichcestablishedbythestericfield(LOO)(47.6%)andelectrostaticfield(52.4%),ther2,q22andrpredwere0.624,0.949and0.410,respectively.ThebestERβCoMSIAmodelisestablishedbyelectrostaticfield(37.8%)and(LOO)hydrogenbonddonor(62.2%),ther2,q2andr2predwere0.611,0.948and0.644,res