Nitric Oxide Photo-Donor Hybrids of Ciprofloxacin and Norfloxacin: A Shift in Activity from Antimicrobial to Anticancer Agents

The potential anticancer
effect of fluoroquinolone antibiotics
has been recently unveiled and related to their ability to interfere
with DNA topoisomerase II. We herein envisioned the design and synthesis
of novel Ciprofloxacin and Norfloxacin nitric oxide (NO) photo-donor
hybrids to explore the potential synergistic antitumor effect exerted
by the fluoroquinolone scaffold and NO eventually produced upon light
irradiation. Anticancer activity, evaluated on a panel of tumor cell
lines, showed encouraging results with IC50 values in the
low micromolar range. Some compounds displayed intense antiproliferative
activity on triple-negative and doxorubicin-resistant breast cancer
cell lines, paving the way for their potential use to treat aggressive,
refractory and multidrug-resistant breast cancer. No significant additive
effect was observed on PC3 and DU145 cells following NO release. Conversely,
antimicrobial photodynamic experiments on both Gram-negative and Gram-positive
microorganisms displayed a significant killing rate in Staphylococcus aureus, accounting for their potential
effectiveness as selective antimicrobial photosensitizers.