Phenothiazinium photosensitisers XI. Improved toluidine blue photoantimicrobials

Abstract

The phenothiazinium derivative toluidine blue O (TBO) is widely employed as a photoantimicrobial agent in clinical trialling, particularly in dentistry. However, its activity against a range of pathogenic microbial species is not significantly different to that of the standard photoantimicrobial methylene blue. In the current study, derivatives of TBO with varying hydrocarbon substitution in chromophore position 2 were synthesised via the established anilinethiosulphonic route, using the mild oxidant silver(II) carbonate to allow substituent preservation.The resulting series of analogues demonstrated the expected increases in visible absorption wavelength and lipophilicity with increasing hydrocarbon content, as well as decreased aggregation for derivatives with bulkier substituents, and all produced singlet oxygen on illumination in vitro. Screening against a range of bacterial and fungal pathogens relevant to infection control showed remarkable increases in activity relative to the parent compound, particularly against the clinically important Gram-negative bacterium Pseudomonas aeruginosa. In addition, in order to demonstrate clinical relevance, the photoactivities of the new derivatives against microbial targets were compared to conventional antibacterial and antifungal drugs, as well as biocides commonly used for local disinfection. Activity here was also generally greater than that of the conventional agents used for comparison, considerably so relative to the local disinfectant agents.

Effects of butyl toluidine blue photosensitizer on antimicrobial photodynamic therapy for experimental periodontitis treatment in rats

“…For the aPDT treatment and PS in the absence of light, irrigation with 0.3 mL BuTB was performed at three concentrations: 0.1 mg/mL, 0.5 mg/mL and 2 mg/mL. The photosensitizer BuTB was synthesized as previously reported (16). Irrigation was carried out with the aid of an insulin syringe, carefully directing the tip of the needle into the tooth / gingival tissue following homeostasis of the area.…”

“…The present study demonstrates for the first time the in vivo effects of three concentrations of a new PS. Butyl toluidine blue (BuTB) was developed by physicochemical modifications of the molecular structure of the established phenothiazine dye toluidine blue O (TBO) (16). Previously evaluated for photoantimicrobial activity (16), BuTB was evaluated here as a photosensitizing agent for in vivo aPDT, as an adjuvant to SRP, in the treatment of experimental periodontitis (EP) in rats.…”

“…Butyl toluidine blue (BuTB) was developed by physicochemical modifications of the molecular structure of the established phenothiazine dye toluidine blue O (TBO) (16). Previously evaluated for photoantimicrobial activity (16), BuTB was evaluated here as a photosensitizing agent for in vivo aPDT, as an adjuvant to SRP, in the treatment of experimental periodontitis (EP) in rats. The effectiveness of BuTB concentration was evaluated on alveolar bone loss by histometric analysis, local regulation of osteoclastogenesis and osteoclastic activity by RANKL and OPG immunolabelling and local recruitment of osteoclasts using TRAP immunolabeling.…”

In vitro susceptibilities of Neoscytalidium spp. sequence types to antifungal agents and antimicrobial photodynamic treatment with phenothiazinium photosensitizers

“…Novel derivatives, such as the pentacyclic S137, and derivatives with basic side chains, more effective than the lead compound MB are still being synthesized [38][39]. Previous studies have reported that APDT with phenothiazinium derivatives kills different fungal structures, such as microconidia of different species including the dermatophyte Trychophyton spp.…”

Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates Against HIV Env-Expressing Cells

“…PSs can be activated by visible light of a specific wavelength to initially form the excited singlet state, followed by transition to the longer-lived excited triplet state (17). This triplet state can undergo photochemical reactions in the presence of oxygen via Type I photochemical mechanisms (electron transfer to produce superoxide, hydrogen peroxide, and hydroxyl radicals), typical of phenothiazinium dyes (18), or Type II mechanisms (energy transfer process), typical of porphyrins (19,20), and Rose Bengal (21,22). Reactive oxygen species (ROS) can oxidize lipids, proteins, and nucleic acids, leading to cell damage and death through necrosis where cells swell and lyse to release their intracellular content causing inflammation, or alternatively cells can undergo apoptosis (23,24).…”