分子模拟技术筛选抗hiv-1逆转录酶活性化合物

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1、screeningmethodhassomereliabiiityandaccuracy．9．Virtualresultsshowthecompoundspossessingthehigherscores．formedhydrogenbondswiththeresiduesLysl01andⅡ一ⅡstackinginteractiOIlSwiththeresiduesTYRl81，TRP229，andhorseshoeshapeddockingconformationmoleculeshavethegreaterpossibilityto

2、inhibitagainsttheHIV一1reversetranscriptase．10．InthiSpaper，the25compoundswastestedbytheanti—IIIV1bioassayinvitro．andtheresultsshowedthatthe25compoundshaveanti—HIV—lacLiviLy，ofwhichtheEC50ofthe10compoundswaslessthanlOug／ml，andtheTIofj一(4fluorophenyl)3[2(11{indol一3一y1)ethyl]

3、thioureaand6一[[5一(4一chloroanilino)一1，3，4一thiadiazol一2一y1]methoxy]一4一methylchromen一2一onewasgreaterthan10．11．Thevirtualandbioassaytestresultsshowedthatthedockingconformationofl一(4一fluorophenyl)一3一[2一(1H—indol一3一y1)ethyl]thioureaWaSwellalignedwiththe1jgandofthecrystalcomplex

4、of2ZDlandpresentedtheUshapedstructure．ItformedthehydrogenbondswiththekeyresidueLysl01andtheⅡ一Ⅱstackinginteractions、viththeconservativeresidueTrp229andthearomaticresidueTyrl81inthebindingpocketofHIV1reversetranscriptasewerealsoobserved．ThebioassayinvitroshowedTheCC50valueo

5、fthecompoundWaSgreaterthani00，itsEC50valuewas4．54ug／ml，anditstherapeuticindex(TI)isgreaterthan18．35．Thedockingconformationof6一[[5一(4一chloroanilino)一l，3．4thiadiazol一2一y1]methoxy]一4-methylchI’olnen一2一onewaspresentedthehorseshoeshapedstructureandwel1alignedwiththeligandinthe

6、crystalcomplex．ItformedthehydrogenbondswiththekeyresidueLysl01、Lysl03andtheⅡ一ⅡstackinginteractionswiththeconservatireresidueTrp229andthearomaticresidueTyrl81inthebindingpocketofHIV——1reversetranscriptasewerealSOobserved．ThebioassayinvitroshowedtheCC50value0fIthecompoundwa

7、sgreaterthan100，theEC50was9．85ug／ml，anditstherapeuticindex(TI)iSgreaterthanlO．i5．TheconclusionthatthevirtualrcsultsareingoodagreementwiththebioassayexperimentfullYprovidesthereljabi¨tyofthevirtualmethod．ConcIUSion：1．Fromthecompoundstructure，theflexihieUandhorseshoeshapeds

8、tructureofnon——nucleosidereversetranscriptaseinhibitorscanadapttothebingdingpocketchangeofthetlI