Open AccessNitric Oxide Photo-Donor Hybrids of Ciprofloxacin and Norfloxacin: A Shift in Activity from Antimicrobial to Anticancer Agents
Author(s) -
Antonino N. Fallica,
Carla Barbaraci,
Emanuele Amata,
Lorella Pasquinucci,
Rita Turnaturi,
Maria Dichiara,
Sebastiano Intagliata,
Marzia Bruna Gariboldi,
Emanuela Marras,
Viviana Teresa Orlandi,
Claudia Ferroni,
Cecilia Martini,
Antonio Rescifina,
Davide Gentile,
Greta Varchi,
Agostino Marrazzo
Publication year - 2021
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.1c00917
Subject(s) - chemistry , antimicrobial , norfloxacin , ciprofloxacin , doxorubicin , du145 , pharmacology , topoisomerase iv , nitric oxide , antibiotics , cancer cell , microbiology and biotechnology , cancer , dna gyrase , biochemistry , escherichia coli , chemotherapy , biology , organic chemistry , lncap , gene , genetics
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 IC 50 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.