TY - JOUR
T1 - Nitric Oxide Photo-Donor Hybrids of Ciprofloxacin and Norfloxacin
T2 - A Shift in Activity from Antimicrobial to Anticancer Agents
AU - Fallica, Antonino Nicolò
AU - Barbaraci, Carla
AU - Amata, Emanuele
AU - Pasquinucci, Lorella
AU - Turnaturi, Rita
AU - Dichiara, Maria
AU - Intagliata, Sebastiano
AU - Gariboldi, Marzia Bruna
AU - Marras, Emanuela
AU - Orlandi, Viviana Teresa
AU - Ferroni, Claudia
AU - Martini, Cecilia
AU - Rescifina, Antonio
AU - Gentile, Davide
AU - Varchi, Greta
AU - Marrazzo, Agostino
N1 - Funding Information:
All the authors gratefully acknowledge the Italian MUR for supporting grant PRIN 2017 (Code 201744BN5T) and PON R&I funds 2014–2020 (CUP: E66C18001320007, AIM1872330, activity 1).
Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society.
PY - 2021/8/12
Y1 - 2021/8/12
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jmedchem.1c00917
DO - 10.1021/acs.jmedchem.1c00917
M3 - Article
C2 - 34319100
AN - SCOPUS:85112714193
VL - 64
SP - 11597
EP - 11613
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 15
ER -