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Indoloquinolizidine Derivatives as Novel and Potent Apoptosis Inducers and Cell‐Cycle Blockers

A collection of approximately 11 000 natural‐product derived and inspired compounds was screened for potential apoptosis inducers in the human tumour cell lines HepG2 (liver), HeLa (cervix) and MCF‐7 (breast) by means of MTT and ATP‐luminescence assays, automated cell counting, caspase 3/7 assay as well as by fluorescence activated cell sorting (FACS) analysis. A group of seven indoloquinolizidine derivatives was identified that exhibited IC50 values for cell proliferation as low as 2 μmol L−1, with no major necrosis of cells detectable. At the same time, an increase in the rate of apoptosis of up to 600 % relative to the reference level was observed. FACS analysis indicated that these effects are related to an arrest of cells in the G2M phase of the cell cycle.