RESUMEN
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.
RESUMEN
OBJECTIVE: To study the synthesis and antitumor activity of novel quinolone derivatives. METHODS: Based on the structure of ciprofloxacin, the objective substances were designed and synthesized according to the principle of fragmentbased drug discovery. Their anti-tumor activities in vitro were evaluated against A549, HL-60, and Hela cells by MTT assay. Molecular docking studies were performed with the Libdock protocol of Discovery Studio to afford the ideal interaction mode of the compound with the binding site of the Topo I. RESULTS: Eight novel compounds were synthesized and showed potential antitumor activities. CONCLUSION: The antitumor activities of the synthesized quinolone derivatives are worthy of further study.
RESUMEN
OBJECTIVE: To synthesize quinolone derivatives and investigate their anti-tumor activities in vitro. METHODS: A series of quinolone derivatives were designed and synthesized from Norfloxacin or Ciprofloxacin with N-(phenylsulfonyl) formimidamide. Their anti-tumor activities in vitro were evaluated for A549, HL-60, Hela cells by MTT assay. Molecular docking studies were performed with the Discovery Studio to afford the ideal interaction mode of the compound into the binding site of the Topo I. RESULTS: Fourteen novel compounds were synthesized and the structures were characterized by H-NMR, ESI and HRMS. MTT assay showed that most quinolone derivatives exhibited some anti-tumor activities. CONCLUSION: These quinolone derivatives are worth further being developed.