Molecules, Vol. 29, Pages 5382: Unveiling the Anticancer Potential of a New Ciprofloxacin-Chalcone Hybrid as an Inhibitor of Topoisomerases I & II and Apoptotic Inducer

Molecules, Vol. 29, Pages 5382: Unveiling the Anticancer Potential of a New Ciprofloxacin-Chalcone Hybrid as an Inhibitor of Topoisomerases I & II and Apoptotic Inducer

Molecules doi: 10.3390/molecules29225382

Authors: Doaa Mohamed Elroby Ali Hossameldin A. Aziz Stefan Bräse Areej Al Bahir Abdullah Alkhammash Gamal El-Din A. Abuo-Rahma Ali M. Elshamsy Hamada Hashem Walid M. Abdelmagid

The current study has yielded promising results in the evaluation of a new ciprofloxacin-chalcone hybrid (CP derivative) for its anticancer activity as potential Topoisomerases (Topo) I and II inhibitors. The in vitro results showed that the CP derivative significantly suppressed the growth of HCT-116 and LOX IMVI cells, with IC50 values of 5.0 μM and 1.3 μM, respectively, outperforming Staurosporine, which had IC50 values of 8.4 μM and 1.6 μM, respectively. Flow cytometry analysis revealed that the new CP derivative triggered apoptosis and cell cycle arrest at the G2/M phase, associated with the up-regulation of pro-apoptotic genes (Bax and Caspase 9) and downregulation of the anti-apoptotic gene (Bcl-2). Further investigations showed that the CP derivative inhibited Topo I and II enzymes, as expected molecular targets; docking studies further supported its dual inhibitory action on Topo I and II. These findings suggest that the ciprofloxacin-chalcone hybrid could be a promising lead compound for developing new anticancer therapy.