Pyrroloquinolinone-based dual topoisomerase I/II inhibitor

• New alkylamino pyrroloquinolinone derivatives were synthesized and studied.
• The compounds showed antiproliferative activity against A431 cell line.
• The compounds were assayed for antitopoisomerase II activity.
• The most active compound 3c was tested also against topoisomerase I.
• Compound 3c demonstrated dual topo I/II inhibitory activity.

A new series of pyrroloquinolinones bearing different alkylamino side chains were synthesized and evaluated as cytotoxic compounds against three different human tumor cell lines (HeLa, HL-60 and A431). Some compounds showed interesting antiproliferative activity, in particular against A431 cells. The compounds were tested for their ability to counteract topoisomerase II relaxation activity and the most interesting one (3c) was tested also against topoisomerase I, resulting a dual inhibitor. The molecular interactions between 3c and the intracellular targets were finally investigated through molecular modeling simulations.

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