Improving Photodynamic Inactivation of Bacteria in Dentistry: Highly Effective and Fast Killing of Oral Key Pathogens with Novel Tooth-Colored Type-II Photosensitizers

• Published in: Journal of medicinal chemistry 2014-06, Vol.57 (12), p.5157-5168
• Main Authors: Späth, Andreas, Leibl, Christoph, Cieplik, Fabian, Lehner, Karin, Regensburger, Johannes, Hiller, Karl-Anton, Bäumler, Wolfgang, Schmalz, Gottfried, Maisch, Tim
• Format: Article
• Language: English
• Subjects: Actinomyces - drug effects; Actinomyces - metabolism; Aggregatibacter actinomycetemcomitans - drug effects; Aggregatibacter actinomycetemcomitans - metabolism; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Color; Drug Stability; Enterococcus faecalis - drug effects; Enterococcus faecalis - metabolism; Gram-Negative Bacteria - drug effects; Gram-Negative Bacteria - metabolism; Gram-Positive Bacteria - drug effects; Gram-Positive Bacteria - metabolism; Periodontitis - microbiology; Phenalenes - chemical synthesis; Phenalenes - chemistry; Phenalenes - pharmacology; Photochemotherapy; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Singlet Oxygen - metabolism; Streptococcus mutans - drug effects; Streptococcus mutans - metabolism; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm4019492

Increasing antibiotic resistances in microorganisms create serious problems in public health. This demands alternative approaches for killing pathogens to supplement standard treatment methods. Photodynamic inactivation of bacteria (PIB) uses light activated photosensitizers (PS) to generate reactive oxygen species immediately upon illumination, inducing lethal phototoxicity. Positively charged phenalen-1-one derivatives are a new generation of PS for light-mediated killing of pathogens with outstanding singlet oxygen quantum yield ΦΔ of >97%. Upon irradiation with a standard photopolymerizer light (bluephase C8, 1260 ± 50 mW/cm2) the PS showed high activity against the oral key pathogens Enterococcus faecalis, Actinomyces naeslundii, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans. At a concentration of 10 μM, a maximum efficacy of more than 6 log10 steps (≥99.9999%) of bacteria killing is reached in less than 1 min (light dose 50 J/cm2) after one single treatment. The pyridinium substituent as positively charged moiety is especially advantageous for antimicrobial action.