Synthesis,biologicalevaluationandmoleculardockingstudiesofnovel14,5dihydro1Hpyrazol1ylethanonecontaining1methylindolderivativesaspotentialtubulinassemblinginhibitors

Synthesis,biologicalevaluationandmoleculardockingstudiesofnovel14,5dihydro1Hpyrazol1ylethanonecontaining1methylindolderivativesaspotentialtubulinassemblinginhibitors.pdf
Aseriesofnovelcompounds(6a-6v)containing1-methylindoland31-(4,5-dihydro-1H-pyrazol-1-yl)ethanoneskeletonweredesigned,synthesizedandbiologicallyevaluatedaspotentialtubulinpolymerizationinhibitorsandanticanceragents.Amongthem,compound6qshowedthemostpotenttubulinpolymerizationinhibitoryactivity(IC50=1.98μM)andinvitrogrowthinhibitoryactivityagainstA549,MCF-7andHepG2celllines,withIC50valuesof0.15μM,0.17μM,and0.25μMrespectively,beingcomparabletothepositivecontrol.Furthermore,compound6qwasapotentinducerofapoptosisinA549cellsandithadtypicalcellulareffectsformicrotubuleinteractingagents,causingarrestofthecellcycleinG2/Mphase.Confocalmicroscopyassayandmoleculardockingresultsfurtherdemonstratedthat6qcouldbindtightlytothecolchicine-siteoftubulinandactasananti-tubulinagent.Thesestudies,alongwith3D-QSARmodelingprovidedanimportantbasisforfurtheroptimizationofcompound6qasapotentialanticanceragent.
作者：Meng-RuYang Ya-JuanQin ChenChen Ya-LiangZhang Bo-YanLi Tian-BaoLiu Hai-BinGong Bao-ZhongWang Hai-LiangZhu
作者单位：StateKeyLaboratoryofPharmaceuticalBiotechnology,NanjingUniversity,Nanjing210093,People'sRepublicofChina2XuzhouCentralHospital,Xuzhou221009,People'sRepublicofChinaXuzhouCentralHospital,Xuzhou221009,People'sRepublicofChina
母体文献：第九届国际分子模拟与信息技术应用学术会议(ICMS&I2018)论文集
会议名称：第九届国际分子模拟与信息技术应用学术会议(ICMS&I2018)  
会议时间：2018年5月1日
会议地点：太原
主办单位：中国化学会,中科院,北京创腾科技有限公司
语种：chi
分类号：
关键词：tubulin  inhibitors  1-methylindol  pyrazoline  moleculardocking
在线出版日期：2019年6月27日
基金项目：
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