| Autor: |
Ali DME; Department of Biochemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt., Aziz HA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, New Valley University, New Valley 72511, Egypt., Bräse S; Institute of Biological and Chemical Systems-Functional Molecular Systems (IBCS-FMS), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany., Al Bahir A; Chemistry Department, Faculty of Science, King Khalid University, Abha 64734, Saudi Arabia., Alkhammash A; Department of Pharmacology, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia., Abuo-Rahma GEA; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, New Minia City 61768, Egypt., Elshamsy AM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, New Minia City 61768, Egypt., Hashem H; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt., Abdelmagid WM; Medicinal Chemistry and Drug Discovery Research Centre, Swenam College, 210-6125 Sussex Avenue, Burnaby, BC V5H 4G1, Canada. |
| Abstrakt: |
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 IC 50 values of 5.0 μM and 1.3 μM, respectively, outperforming Staurosporine, which had IC 50 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. |
