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Regio- and stereoselective synthesis of dispirooxindole-pyrrolocarbazole hybrids via 1,3-dipolar cycloaddition reactions: Cytotoxic activity and SAR studies
European Journal of Medicinal Chemistry ( IF 6.7 ) Pub Date : 2017-11-20 , DOI: 10.1016/j.ejmech.2017.11.039
Karunanidhi Murali , Hazel A. Sparkes , Karnam Jayarampillai Rajendra Prasad

A library of novel dispiro compounds containing oxindole-pyrrolo-carbazole hybrid frame works has been synthesized in a fully regio- and stereoselective fashion by the three-component 1,3-dipolar cycloaddition of azomethineylides generated in situ from the condensation of isatins and benzylamine with 2-arylidene/heteroarylidene-2,3,4,9-tetrahydro-1H-carbazole-1-one. The structures of the compounds were established by FT-IR, 1H NMR, 13C NMR, X-ray diffraction and elemental analysis. The synthesized dispiro heterocycles have been screened for in vitro cytotoxic activity by MTT assay and displayed enviable growth inhibition on both the cancer cell lines i.e. breast cancer cell line MCF-7 and lung cancer cell line A-549. Morphological changes and apoptosis induction have been studied by inverted light microscopic, fluorescent microscopic techniques and by flow cytometry analyses. The preliminary structure activity relationships were also carried out. Data indicated that among dispiro-carbazole compounds,6-chloro-4'-(thiophen-2-yl)-5′-phenyl-3,4-dihydrodispiro[carbazole-2,3′-pyrrolo-2′,3″-indole]-9(H)-1,2″-dione 7e could be exploited as a significant therapeutic drug against breast cancer as well as lung cancer cell proliferation.



中文翻译:

通过1,3-偶极环加成反应的区域和立体选择性合成dispirooxindole-吡咯并咔唑杂种:细胞毒活性和SAR研究

通过由靛蓝和苄胺与三聚氰胺的缩合反应原位生成的偶氮甲亚胺的三组分1,3-偶极环加成反应,以完全区域选择性和立体选择性的方式合成了一个包含二氢吲哚-吡咯并咔唑混合骨架的新型双螺化合物的库。2-亚芳基/杂亚芳基-2,3,4,9-四氢-1 H-咔唑-1-一。通过FT-IR,1 H NMR,13 C NMR,X射线衍射和元素分析确定化合物的结构。已对合成的双螺杂环化合物进行了体外筛选通过MTT测定具有细胞毒性活性,并且对癌细胞系,即乳腺癌细胞系MCF-7和肺癌细胞系A-549显示出令人羡慕的生长抑制。已经通过倒置光学显微镜,荧光显微镜技术和流式细胞仪分析研究了形态学变化和细胞凋亡诱导。初步的结构活动关系也进行了。数据表明,在二螺并咔唑化合物中,6-氯-4'-(噻吩-2-基)-5'-苯基-3,4-二氢二螺并[咔唑-2,3'-吡咯并2',3″-吲哚] -9(H)-1,2“-二酮7e可作为抗乳腺癌以及肺癌细胞增殖的重要治疗药物。

更新日期:2017-11-20
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