双吲哚,β-氨基酮及硫醚类化合物的合成和生物活性分析-synthesis and biological activity analysis of bis - indoles, β - aminoketones and thioethers.docxVIP

摘要摘要本文设计合成了三类具有新颖结构的双吲哚类，β-氨基酮类和硫醚类化合物。所合成的目标化合物的结构由核磁共振氢谱及碳谱、高分辨质谱、红外光谱等确证。并对合成的目标化合物的抗真菌或抗癌活性进行了测试。为寻找结构新颖的双吲哚的抗癌先导化合物，合成了3,4-二吲哚硫色满酮(或二氢噻喃)类化合物，通过MTT法检测所有化合物对七种癌细胞增殖的抑制活性，结果表明大部分化合物对受试癌细胞都有抑制活性，其中化合物Ⅰ5a对MCF7的半数最大抑制浓度（IC50）值为7.798μg/mL，化合物Ⅰ5a在100μmol时其抑制活性可与依托泊苷（VP-16）的抑制活性相当，其余的化合物也表现出对拓扑异构酶Ⅱ不同程度的抑制活性。采用简单、高效、快捷的一锅法合成β-氨基酮类化合物。在醋酐、80℃的条件下，以硅胶硫酸为催化剂，通过苯甲醛、硫色满酮、乙腈三组分缩合而得到3-乙酰氨基苯甲基硫色满酮。体外抗真菌活性测试结果表明，此类化合物对石膏样小孢子菌表现出不同程度的抑菌作用。硫醚类化合物是通过苯硫酚，芳香醛和5,5-二甲基-1,3-环己二酮在DBSA催化下的一锅法反应得到。通过催化剂、温度和原料比率选择最佳反应条件。初步的生物活性测试结果表明，部分化合物对新生隐球菌，白色念珠菌，红色毛癣菌和烟曲霉菌有温和的抗真菌活性。关键词：双吲哚，β-氨基酮，硫醚，抗真菌，抗癌，拓扑异构酶Ⅱ，MTT法AbstractAbstractThreenoveltypecompoundsweredesignedandsynthesizedinthispaper:disindolecompounds,β-aminoketonescompoundsandthioethercompounds.ThestructuresofsynthesizedcompoundswerecharacterizedbyIR,HRMS,1HNMR,and13CNMR.Biologicalactivitiesofthetargetcompoundsweretested.Inanefforttodeveloppotentanticanceragents,anovelseriesofbisindolylalkanesanaloguessuchas3,3’-(thiochroman-4,4-diyl)bis(1H-indole)aresynthesized.Anti-proliferat-iveactivitiesforallofthesecompoundsareinvestigatedbythemethodofMTTassayon7humancancerlines.Mostofthemshowedantitumoractivitiesinvitro,thehalfmaximalinhibitoryconcentration(IC50)valueis7.798μg/mLofⅠ5aagainstMCF7.Compound5ashowedcomparabletopoisomeraseIIinhibitoryactivitytoetoposide(VP-16)at100μMconcentration.TherestofthecompoundsalsoshowedvaryingdegreetopoisomeraseIIinhibitoryactivity.Inthispaperwehavedesignedasimple,efficient,fastmethodologyfortheone-potsynthesisofβ-aminoketonederivativessuchasN-[(4-oxo-thiochroman-3-yl)-phenyl-methyl]-acetamidebycouplingthreecomponents,viabenzaldehyde,thiochromanoneandacetonitrileinthepresenceofaceticanhydrideandcatalyzedbysilicasulfuricacidat80℃.TheinvitroantifungalactivitytestresultsofthetargetcompoundsshowedthatthecompoundshadvaryingdegreeantibacterialeffectsonM.gypseum.Thethioethercompoundwassynthesizedbyone-potreactionfromthiophenol,aromaticaldehydeand5,5-dimethyl-1,3-cyclohexanedionecatalyzedbyDBSA.Itwasdeterminedtheoptimumcond