The Development and Evaluation of a Range of Phototherapeutic Dyes Towards Infection Control

Abstract

The rise in antimicrobial resistance is threatening modern healthcare treatments, such as organ transplants and chemotherapy, due to the immunosuppressive nature of these procedures and the resulting dependency on antimicrobials. The discovery of new antimicrobial agents is happening at a too slow rate to deal with the rapidly emerging resistant microbes. Photodynamic therapy is an up and coming treatment for topical infections, involving the use of a dye in combination with a light source. Patients who suffer burn wounds are at a higher risk of acquiring an antimicrobial infection due to the immunosuppressive nature of the burn wound site, making infections one of the main causes of deaths in burn patients. The potential use of photodynamic therapy as a treatment for topical infections could potentially help to reduce the amount of deaths caused by infections in burns patients.
During this study a variety of photoactive dyes, belonging to either the flavin, porphyrin or anthraquinone family were synthesised. These dyes were tested to determine the singlet oxygen yield and how the change in the structure affected the singlet oxygen production. The growth inhibition of these compounds were also tested to see how the changing the derivative affected the growth inhibition of each family of compounds. The singlet oxygen and growth inhibition testing was carried out to see if there was a particular derivative or family of compounds which performed better than the other families.
During this study there was a total of 35 dye compounds synthesised which belonged to either the flavin, porphyrin or anthraquinone families. The singlet oxygen production was tested by monitoring the decolourisation of TPCPD. When comparing the half-lives of the compounds the porphyrin derivatives and hydroxy anthraquinone derivatives had the lowest half-life. The growth inhibition data was obtained by testing the compounds in vitro against C.albicans, with only four compounds showed antimicrobial activity. The 5,10,15,20-Tetrakis-(4-hydroxyphenyl)-21H,23H-porphine was the only porphyrin to show moderate growth inhibition when illuminated with blue light for 20 minutes. All the hydroxy anthraquinone derivatives showed antimicrobial activity with the hydroxy anthraquinone and hydroxy bianthrone derivatives having a lower minimum inhibitory concentration when compared with fluconazole when illuminated with blue light. The hydroxy anthrone also showed the same minimum inhibitory concentration has fluconazole when illuminated with blue light.