用比较分子力场分析法研究青蒿素醚类和酯类衍生物的三维定量结.pdfVIP

BIBLID ISSN ActaPharmacologicaSmica 十 国药理学报 3D—QSAR studyonetherandesteranalogsofartemisininwith comparativemolecularfieldanalysis JIANG Hua—Liang．CHEN Kai—Xian，WANG Hong—W u，TANG Yun，CHEN Jian—Zhong JIRu—Yun (ShanghaiInstituteofMateriaMedica，ChineseAcademyofSciences， Shahrghai200032，CKina) ABSTRACT Comparative molecular field majorIcadinanareawhereresistancetoexist— analysis (Co M FA )，athree—dimensionalquan— ing drug treatment is increasing alarm ing— titative structure—activjty relationshjP (3D— lv 一”． QSAR)paradigm ，wasusedtostudythecot— 0urInstitutehasmodified thestructure relationsbetween thephysicochem icalproper— of1andsynthesizedaseriesofetherandester ties and the witro activities ofa series of derivativescn． W ith pharmacological screen， etherand esteranalogsofartem isinin． Four thequantitativebiologicalactivity，designated alignmentmodelswereusedjntheCoM FA in— by SDg0(Fig 1)，was determined ． Dihy— vestigation． The correlations derived from droartemisinin (2) and its ether and ester CoM FA analysis w ith the four alignments analogs (3)weremoreactivethan 1． proved all to have good predictive values． In ourpreviousstudies on the etherand Thestericfieldpredictivemodelofalignment ester analogs of artem isinin w ith quantum B isaccordantwiththeexperimentalresultsof chemicalmethods，wehavesuggestedaphar— AveryM A ，etal：JMed Chem 1993{36： macophore and an interaction modelof the 4264— 75 The electrostatic field predictive drugswith receptor ． In 、order to demon— resultsofalignmentsA ，B，andC areconsist— strate the relationship between the three— entw ithourpreviousresultofquantum chem— dimensionaIstructurepropertiesandtheactiv- icaIcalculation． The higbest，：… ofalign— jties in vitro，we carried out a three—dimen- mentD ，indicated thatthesidechain of…C sion