Unveiling the Anticancer Potential of a New Ciprofloxacin-Chalcone Hybrid as an Inhibitor of Topoisomerases I & II and Apoptotic Inducer
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
Affiliations
Doaa Mohamed Elroby Ali
Department of Biochemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt
Hossameldin A. Aziz
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, New Valley University, New Valley 72511, Egypt
Stefan Bräse
Institute of Biological and Chemical Systems—Functional Molecular Systems (IBCS-FMS), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany
Areej Al Bahir
Chemistry Department, Faculty of Science, King Khalid University, Abha 64734, Saudi Arabia
Abdullah Alkhammash
Department of Pharmacology, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia
Gamal El-Din A. Abuo-Rahma
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
Ali M. Elshamsy
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, New Minia City 61768, Egypt
Hamada Hashem
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt
Walid M. Abdelmagid
Medicinal Chemistry and Drug Discovery Research Centre, Swenam College, 210-6125 Sussex Avenue, Burnaby, BC V5H 4G1, Canada
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.
