期刊论文详细信息
Journal of Enzyme Inhibition and Medicinal Chemistry
Synthesis, molecular modelling and anticancer evaluation of new pyrrolo[1,2-b]pyridazine and pyrrolo[2,1-a]phthalazine derivatives
Violeta Mangalagiu1  Ramona Danac2  Lacramioara Popovici2  Roxana-Maria Amarandi2  Ionel I. Mangalagiu2 
[1] CERNESIM Research Centre, Alexandru Ioan Cuza University of Iasi, Iasi, Romani;Faculty of Chemistry, Alexandru Ioan Cuza University of Iasi, Iasi, Romania;
关键词: Anticancer;    phenstatin;    b;    a;    3 + 2 dipolar cycloaddition;    docking;    N-heterocycles;   
DOI  :  10.1080/14756366.2018.1550085
来源: publisher
PDF
【 摘 要 】

Two new series of heterocyclic derivatives with potential anticancer activity, in which a pyrrolo[1,2-b]pyridazine or a pyrrolo[2,1-a]phthalazine moiety was introduced in place of the 3′-hydroxy-4′-methoxyphenyl ring of phenstatin have been synthesised and their structure-activity relationship (SAR) was studied. Fourteen of the new compounds were evaluated for their in vitro cytotoxic activity by National Cancer Institute (NCI) against 60 human tumour cell lines panel. The best five compounds in terms of in vitro growth inhibition were screened in the second stage five dose-response studies, three of them showing a very good antiproliferative activity with GI50<100 nM on several cell lines including colon, ovarian, renal, prostate, brain and breast cancer, melanoma and leukemia. Docking experiments on the biologically active compounds showed a good compatibility with the colchicine binding site of tubulin.

【 授权许可】

CC BY   

【 预 览 】
附件列表
Files Size Format View
RO202004230842928ZK.pdf 1856KB PDF download
  文献评价指标  
  下载次数:1次 浏览次数:1次