TY - JOUR
T1 - Regio- and stereoselective synthesis of dispirooxindole-pyrrolocarbazole hybrids via 1,3-dipolar cycloaddition reactions
T2 - Cytotoxic activity and SAR studies
AU - Murali, Karunanidhi
AU - Sparkes, Hazel A.
AU - Rajendra Prasad, Karnam Jayarampillai
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - 1,3-Dipolar cycloaddition
KW - Anti-proliferative
KW - Apoptosis
KW - Azomethineylide
KW - Flow cytometry
UR - http://www.scopus.com/inward/record.url?scp=85036552056&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2017.11.039
DO - 10.1016/j.ejmech.2017.11.039
M3 - Article (Academic Journal)
C2 - 29197734
AN - SCOPUS:85036552056
SN - 0223-5234
VL - 143
SP - 292
EP - 305
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -