典型文献
Design,synthesis,and evaluation of fluoroquinolone derivatives as microRNA-21 small-molecule inhibitors
文献摘要：
MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone de-rivatives Al-A43 were synthesized and used as miRNA-21 inhibitors.Compound A36 showed the most potent inhibitory activity and specificity for miRNA-21 in a dual-luciferase reporter assay in HeLa cells.Compound A36 significantly reduced the expression of mature miRNA-21 and increased the protein expression of miRNA-21 target genes,including programmed cell death protein 4(PDCD4)and phos-phatase and tensin homology deleted on chromosome ten(PTEN),at 10 uM in HeLa cells.The Cell Counting Kit-8 assay(CCK-8)was used to evaluate the antiproliferative activity of A36;the results showed that the IC50 value range of A36 against six tumor cell lines was between 1.76 and 13.0 μM.Meanwhile,A36 did not display cytotoxicity in BEAS-2B cells(lung epithelial cells from a healthy human donor).Furthermore,A36 significantly induced apoptosis,arrested cells at the G0/G1 phase,and inhibited cell-colony formation in HeLa cells.In addition,mRNA deep sequencing showed that treatment with A36 could generate 171 dysregulated mRNAs in HeLa cells,while the expression of miRNA-21 target gene dual-specificity phosphatase 5(DUSP5)was significantly upregulated at both the mRNA and protein levels.Collectively,these findings demonstrated that A36 is a novel miRNA-21 inhibitor.
文献关键词：
中图分类号：
作者姓名：
Yuan-Yuan Hei;Si Wang;Xiao-Xiao Xi;Hai-Peng Wang;Yuanxu Guo;Minhang Xin;Congshan Jiang;Shemin Lu;San-Qi Zhang
作者机构：
Department of Medicinal Chemistry,School of Pharmacy,Xi'an Jiaotong University Health Science Center,Xi'an,710061,China;Key Laboratory of Environment and Genes Related to Diseases(Xi'an Jiaotong University),Ministry of Education,Xi'an,710061,China;Institute of Molecular and Translational Medicine(IMTM),and Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Xi'an Jiaotong University Health Science Center,Xi'an,710061,China;Department of Medical Oncology,Shaanxi Provincial People's Hospital,Xi'an,710068,China
文献出处：
引用格式：
[1]Yuan-Yuan Hei;Si Wang;Xiao-Xiao Xi;Hai-Peng Wang;Yuanxu Guo;Minhang Xin;Congshan Jiang;Shemin Lu;San-Qi Zhang-.Design,synthesis,and evaluation of fluoroquinolone derivatives as microRNA-21 small-molecule inhibitors)[J].药物分析学报（英文）,2022(04):653-663
A类：
A43,uM
B类：
Design,synthesis,evaluation,fluoroquinolone,derivatives,microRNA,small,molecule,inhibitors,MicroRNA,miRNA,highly,expressed,various,tumors,Small,inhibition,considered,attractive,novel,cancer,therapeutic,strategy,In,this,study,were,synthesized,used,Compound,A36,showed,most,potent,inhibitory,activity,specificity,dual,luciferase,reporter,assay,HeLa,cells,significantly,reduced,expression,mature,increased,protein,target,genes,including,programmed,death,PDCD4,tensin,homology,deleted,chromosome,PTEN,Cell,Counting,Kit,CCK,was,evaluate,antiproliferative,results,that,IC50,value,range,against,six,lines,between,Meanwhile,did,not,display,cytotoxicity,BEAS,2B,lung,epithelial,from,healthy,human,donor,Furthermore,induced,apoptosis,arrested,G0,G1,phase,inhibited,colony,formation,addition,deep,sequencing,treatment,could,generate,dysregulated,mRNAs,phosphatase,DUSP5,upregulated,both,levels,Collectively,these,findings,demonstrated
AB值：
0.568476
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