二芳基亚甲基环烷烃类微管蛋白抑制剂的设计、合成及抗肿瘤活性研究的综述报告摘要：二芳基亚甲基环烷烃类微管蛋白抑制剂在肿瘤治疗中具有重要的作用。本文从设计、合成和抗肿瘤活性三方面综述了二芳基亚甲基环烷烃类微管蛋白抑制剂的研究进展。设计方面主要包括分子对接、分子动力学模拟等。合成方面介绍了二芳基亚甲基环烷烃类微管蛋白抑制剂的多种合成方法。抗肿瘤活性则从体外、体内和临床研究三个方面进行的综述。最后探讨了该类抑制剂的研究方向及其未来发展的前景。关键词：二芳基亚甲基环烷烃类微管蛋白抑制剂;分子对接;分子动力学模拟;合成方法;抗肿瘤活性IntroductionMicrotubulesareessentialcytoskeletalpolymersthatplayacriticalroleincelldivisionanddifferentiation(Katsetosetal.,2003).Microtubule-targetingagents(MTAs)thatinhibitthedynamicsofmicrotubuleshaveemergedaspromisinganticanceragents(Guptaetal.,2021).Amongthem,thediheptyl-substitutedstilbenes,particularlycombretastatinA4,havebeenfoundtopossesspotentantimitoticactivity(Pettitetal.,1988).Thediheptyl-substitutedstilbenesareafamilyoftubulinbindersthatbelongtotheclassofmicrotubule-depolymerizingagents,whichareknownfortheirabilitytoinhibittubulinassemblyviathedestabilizationofmicrotubules(Pettitetal.,1988).Inrecentyears,considerableattentionhasbeenfocusedondesigningandsynthesizingdiheptyl-substitutedstilbenesandothermicrotubule-targetingagentsasanticanceragents.Inthisreview,wesummarizetherecentadvancementsinthedesign,synthesis,andanticanceractivityofdiheptyl-substitutedstilbenes,withaparticularfocusontheirapplicationsincancertherapy.DesignStrategiesDesigningMTAswithhighpotencyandselectivityremainsasignificantchallenge.Overtheyears,variouscomputationaltools,suchasmoleculardockingandmoleculardynamicssimulations,havebeenwidelyemployedfortherationaldesignofMTAs.Moleculardockinginvolvestheuseofcomputationalalgorithmstodocksmallmoleculeinhibitorsintotheactivesiteofthetargetproteintopredicttheirbindingaffinityandorientation(Kolbetal.,2011).Moleculardynamicssimulations,ontheotherhand,useasetofmathematicalalgorithmstosimulatethemovementsofatomsandmoleculesovertime(Fredericketal.,2015).Severalstudieshaveusedthesetoolstodesignandoptimizediheptyl-substitutedstilbenesandotherMTAs(Chowdhuryetal.,2019;Guptaetal.,2021).SynthesisStrategiesSeveralsyntheticstrategieshavebeendevelopedforthesynthesisofdiheptyl-substitut