Simultaneous photoactivation of a fluoroquinolone antibiotic and nitric oxide with fluorescence reporting

Author(s)

Martins, Tassia J. ; Parisi, Cristina ; Pinto, Juliana Guerra ; Brambilla, Isabelle de Paula Ribeiro ; Melilli, Barbara ; Aleo, Danilo ; Ferreira-Strixino, Juliana ; Sortino, Salvatore

• Document type: Journal article
• Source: JOURNAL OF MATERIALS CHEMISTRY B; v. 12, n. 31, p. 9-pg., 2024-07-09.

Abstract

The achievement of smart pharmaceuticals whose bioactivity can be spatiotemporally controlled by light stimuli is known as photopharmacology, an emerging area aimed at improving the therapeutic outcome and minimizing side effects. This is especially attractive for antibiotics, for which the inevitable development of multidrug resistance and the dwindling of new clinically approved drugs represent the main drawbacks. Here, we show that nitrosation of the fluoroquinolone norfloxacin (NF), a broad-spectrum antibiotic, leads to the nitrosated bioconjugate NF-NO, which is inactive at the typical minimum inhibitory concentration of NF. Irradiation of NF-NO with visible blue light triggers the simultaneous release of NF and nitric oxide (NO). The photouncaging process is accompanied by the revival of the typical fluorescence emission of NF, quenched in NF-NO, which acts as an optical reporter. This permits the real-time monitoring of the photouncaging process, even within bacteria cells where antibacterial activity is switched on exclusively upon light irradiation. The mechanism of photorelease seems to occur through a two-step hopping electron transfer mediated by the lowest triplet state of NF-NO and the phosphate buffer ions or aminoacids such as tyrosine. Considering the well-known role of NO as an "unconventional" antibacterial, the NF-NO conjugate may represent a potential bimodal antibacterial weapon activatable on demand with high spatio-temporal control. Light excitation of the nitrosated and inactive form of the antibiotic norfloxacin triggers the release of the antibacterial NO and liberates the active drug restoring its typical fluorescence emission, which acts as an optical self-reporter. (AU)

• FAPESP's process: 22/10251-0 - EVALUATION OF PHOTODYNAMIC THERAPY WITH DIFFERENT COMPOUNDS FOR MICROBIAL INACTIVATION - IN VITRO AND IN VIVO ASSAYS
• Grantee: Juliana Guerra Pinto
• Support Opportunities: Regular Research Grants