A series of water-soluble photosensitizers based on 3-cinnamoylcoumarin for in vitro antimicrobial photodynamic inactivation

Abstract

A series of novel water-soluble photosensitizers (PSs; M1-M5) based on 3-cinnamoylcoumarin derivatives, incorporating carboxylic acid salt (M1, M2), pyridine salt (M3, M4) and quaternary ammonium salt (M5) groups, were designed and synthesized. Their photophysical and photochemical properties and in vitro antimicrobial photodynamic inactivation (PDI) were investigated. M2, modified with two carboxylic acid salts, was unstable in phosphate-buffered saline (PBS). The four other PSs all showed higher binding/uptake to methicillin-resistant Staphylococcus aureus (MRSA), A. baumannii and C. albicans compared with the clinical drug methylene blue (MB), except for M1 to A. baumannii. Furthermore, the three cationic PSs (M3-M5) exhibited equivalent antibacterial PDI efficacies against MRSA and A. baumannii compared with MB. The antifungal efficacies of M4 and M5 to C. albicans were both significantly higher than that of MB, especially for M5, indicating that the quaternary ammonium-salt-modified coumarin derivative has substantial potential for antifungal PDI.

Fig. 1. Synthetic routes to targeted PSs M1–M5.

Fig. 2. Absorption (A) and fluorescence (B) spectra of PSs M1–M5 in PBS (5.0 × 10⁻⁵ mol L⁻¹).

Fig. 3. Photostability of M1–M5 with irradiation time in DMF solution.

Fig. 4. The cellular uptakes of PSs M1, M3–M5 and reference MB by MRSA, A. baumannii (A) and C. albicans (B).

Fig. 5. Relative cell viability of three strains MRSA (A), A. baumannii (B) and C. albicans (C) after being irradiated with laser (40 mW cm⁻²) for 10 min and then incubated with PSs M1, M3–M5 and MB for another 24 h. The error bars denote the standard deviation of three replicates.