Regio- and stereoselective synthesis of dispirooxindole-pyrrolocarbazole hybrids via 1,3-dipolar cycloaddition reactions: Cytotoxic activity and SAR studies

摘要

Abstract 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-1 H -carbazole-1-one. The structures of the compounds were established by FT-IR, 1 H NMR, 13 C 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. Graphical abstract Display Omitted Highlights ? The dispiro hybrid compounds were synthesized in a fully regio- and stereoselective fashion. ? Compounds showed selective growth inhibition on both MCF-7?cell line and A-549?cell line. ? Tested cells were visualized using fluorescent microscopic technique. ? The preliminary structure activity relationships were also established. ? Chloro substituted dispirooxindole-pyrrolo-carbazole exploited as a significant therapeutic drug.