In Vitro Photodynamic Activity of 5,15‐bis(3‐Hydroxyphenyl)porphyrin and Its Halogenated Derivatives Against Cancer Cells

Abstract

5,15-Diarylporphyrins (1-5) with hydroxyl groups and halogens as substituents were prepared by condensation between unsubstituted dipyrromethane and halogenated m-hydroxybenzaldehydes. Photophysical properties show that the nonhalogenated porphyrin 1 has higher fluorescence yield but lower singlet oxygen formation quantum yield than the halogenated derivatives due to the heavy atom effect. The in vitro activity of these derivatives was tested against WiDr colorectal adenocarcinoma and A375 melanoma cancer cells. All porphyrins present a much higher phototoxicity than Photofrin with IC(50) values lower than the 50 nM level for WiDr cells and 25 nM level for A375 cancer cells. The most photoactive compound is the nonhalogenated porphyrin 1 which also presents the highest uptake. Halogenated derivatives present much lower uptakes than 1. However, their photoactivity is similar to compound 1 showing that their intrinsic photoactivity (ISP) is very high. Iodinated compound 4 presents the highest ISP. The greater ability of these porphyrins to destroy cancer cells could be related to their photophysical and photochemical properties.

2-Bromo-5-hydroxyphenylporphyrins for photodynamic therapy: Photosensitization efficiency, subcellular localization and in vivo studies

“…Encouraging preclinical results were reported by Serra and co-workers [13,15] in which a series of tetraaryl and diaryl-substituted hydroxyl substituted porphyrins with halogen groups show high phototoxicity in the in vitro preliminary screening. In the present study we focus on the most active compounds from these studies, which structures are presented in Fig.…”

“…Tetraarylporphyrins with hydroxyl substituents in the phenyl groups proved to be particularly active [10][11][12] but diarylporphyrins prove to be advantageous, being less voluminous molecules with lower molecular weight that can allow higher uptake and quicker clearance [12][13][14].…”

Proteomics displays cytoskeletal proteins and chaperones involvement in Hedyotis corymbosa-induced photokilling in skin cancer cells

“…As shown in Figure S1, the absorption spectrum of H. corymbosa extracts in ethanol shows the typical Soret band at 420 nm and Q band at 670 nm. It suggests a tetrapyrrolic structure, likely present in a mixture of substances, such as chlorins and porphyrin (16,17). The photosensitizing activity of napthodianthrones and tetrapyrrolic derivatives found in plants has been discovered.…”

“…Photodynamic effect occurs when light‐activated photosensitizers transfer the energy to oxygen nearby to produce singlet oxygen. Singlet oxygen can then react with biological substrates, resulting in cellular damage (16,17). Therefore, reactive oxygen species (ROS) may play an important role in the H. corymbosa extracts‐induced photokilling in M21 cells.…”

mTHPC – A drug on its way from second to third generation photosensitizer?

“…A number of arylhalogenated derivatives of 5,15-bis(3-hydroxyphenyl)porphyrin were tested as well. Although the compounds showed higher in vitro activity than Photofrin, halogenation resulted in a lower uptake [36].…”