Antimicrobial Photosensitizers: Drug Discovery Under the Spotlight

Although photodynamic therapy (PDT) was discovered over a hundred years ago by its ability to destroy microorganisms, it has been developed mainly as a cancer therapy. In recent years, due to the inexorable rise in multi-antibiotic resistant strains of pathogens, PDT is being considered as a versatile antimicrobial approach to which microbial cells will not be able to develop resistance. The goal of this review is to survey the different classes of chemical compounds that have been tested as antimicrobial photosensitizers. Some of these compounds have been known for many years, while others have been rationally designed based on recently discovered structural principles. Tetrapyrrole-based compounds (some of which are approved as cancer therapies) that efficiently generate singlet oxygen are more efficient and broad-spectrum when they bear cationic charges, As the macrocycle structure moves from porphyrins to chlorins to phthalocyanines to bacteriochlorins the long wavelength absorption moves to the near-infrared where tissue penetration is better. Four main types of natural products have been tested: curcumin, riboflavin, hypericin and psoralens. Phenothiazinium dyes, such as methylene blue and toluidine blue, have been tested, and some are clinically approved. A variety of non-phenothiazinium dyes with xanthene, triarylmethane and indocyanine structures have also been tested. New ring structures based on BODIPY, squaraine and fullerene cages can also mediate antimicrobial PDT. Finally the process of photocatalysis using titanium dioxide can also have medical uses. Designing new antimicrobial photosensitizers is likely to keep chemists engaged for a long time to come.