Antimicrobial Photosensitizers: Drug Discovery Under the Spotlight

Abstract

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.

Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy

“…[232][233][234] Fullerene-based photodynamic therapy was used for skin-based disease treatment with the bioactive compounds, such as curcumin. 235,236 However, further study on the application of various phyto-derived bioactive compounds with fullerenes in cosmeceutical-based skin therapy has yet to be carried out. This will give way for the development of the new cosmeceutical products with better protective activity by the carrier and bioactive compounds.…”

Photoantimicrobials and Photodynamic Antimicrobial Therapy in Search of Antibiotics

“…Daha sonraki yıllarda FDAT ile ilgili çalışmalar hız kazanmış ve fotofrin (porfimer sodyum) 1993'te Kanada'da, 1995 yılında ise diğer ülkeler de dahil olmak üzere Amerika'da kullanıma girmiş ve Amerika'da Food and Drug Administration'dan (FDA) klinik kullanım izni almıştır (1,3) . Fotofrinin klinik kullanıma girmesiyle birlikte özellikle son 20 yılda enfeksiyon hastalıklarıyla mücadele-de alternatif bir yaklaşım olarak FDAT ile ilgili çalışmaların sayısında artış olmuş-tur (3,30,38,53) .…”

“…Etki ettiği mikroorganizmanın antibiyotiğe dirençli ve duyarlı olanları üzerine eşit dağılım gös-termektedir. Bu nedenle uygulandığı bölge-de organizmanın tamamıyla yok edilmesi söz konusudur (26,47,53) . S.aureus ve MRSA, K.pneumoniae, NDM-1 ve GSBL üreten E.coli'nin zararsız ışıkla aktive edilen katyonik fotoantimikrobiyallere karşı duyarlı olduğu bildirilmektedir (21,47) .…”

“…Kullanılan FS ajan, ışık ile uyarılarak hücrede reaktif oksijen türlerinin (ROS: reactive oxygen species) miktarını arttırmaktadır. Böylece, oluşan oksidatif reaksiyonlar sonucu, mikroorganizmada geri dönüşümsüz olarak ölümcül hasar meydana gelmektedir (1,46,47,53) . Günümüzde esas olarak kanser (özel-likle baş boyun kanserleri) tedavisinde kullanılan fotodinamik tedavi (FDT); dermatoloji, oftalmoloji, gastroenteroloji, kardiyoloji gibi alanlarda da kullanılmaktadır.…”

Modulation of 5-Aminolevulinic acid mediated photodynamic therapy induced cell death in a human lung adenocarcinoma cell line

“…PDT is a minimally invasive therapeutic procedure applied for obstructive, superficial and endoscopically accessible tumors as well as premalignant and non oncological disorders [1][2][3]. It involves the administration of a photosensitizing drug (PS) -often a porphyrin -which is selectively accumulated in malignant tissue.…”