Synthesis and X-ray study of dispiro 8-nitroquinolone analogues and their cytotoxic properties against human cervical cancer HeLa cells

MedChemComm
2019.0

Abstract

A series of unique dispiro analogues containing an oxindole pyrrolidine 8-nitroquinolone hybrid has been obtained through a one-pot three-component 1,3-dipolar cycloaddition of azomethine ylides generated <i>in situ</i> from the condensation of isatins and benzylamine with (<i>E</i>)-3-arylidene-2,3-dihydro-8-nitro-4-quinolones. The structures of the newly synthesized compounds were characterized by using different spectroscopic techniques and by X-ray diffraction studies of their regio- and stereochemistry. All the synthesized compounds were screened for <i>in vitro</i> cytotoxic activity against the human cervical cancer cell line HeLa. The compounds have exhibited potent inhibition against human cervical cancer cells and insignificant toxicity to normal cells. The compounds <b>6d</b>, <b>6a</b>, <b>6h</b>, <b>6b</b>, and <b>6e</b> induced apoptosis of HeLa cells, through ROS influx. The expression levels of proteins involved in the mitochondrion-related pathways were detected, and Western blot analysis showed that apoptosis occurred <i>via</i> activation of caspase-3.

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