Synthesis of Water-Soluble Thioglycosylated <i>trans</i>-A₂B₂ Type Porphyrins: Cellular Uptake Studies and Photodynamic Efficiency

Abstract

The synthesis of water-soluble thioglycosylated A₂B₂ type porphyrins and their zinc(II) complexes is reported. The water-soluble <i>trans</i>-A₂B₂ porphyrins were synthesized in two steps, via [2+2] condensation between thioglycosylated dipyrromethanes and aromatic aldehydes in 15-21% yields. The thioglycosylated <i>trans</i>-A₂B₂ porphyrins showed decent <i>in vitro</i> singlet oxygen generation, which was supported by the intracellular DCFDA study. The <i>in vitro</i> cellular investigations of thioglycosylated A₂B₂ porphyrins were carried out in lung cancer cells (A549) to test their photodynamic therapeutic (PDT) activity. The PDT study revealed significant cytotoxicities of porphyrins with IC₅₀ values between 23.3 and 44.2 μM in the dark, whereas, after visible light exposure, the photosensitizers exhibited IC₅₀ values around 11.1-23.8 μM. The water-soluble thioglycosylated zinc(II) porphyrins having two <i>meso-N</i>-butylcarbazole groups exhibited an excellent degree of photocytotoxicity (IC₅₀ = 4.6-8.8 μM). The flow cytometry analysis revealed that cellular uptake and ROS (reactive oxygen species) generation efficiency of water-soluble thioglycosylated zinc(II) porphyrins were considerably higher than nonmetalated porphyrins. Confocal microscopy images displayed substantial distribution in the endoplasmic reticulum with partial colocalization in mitochondria and lysosomes of water-soluble thioglycosylated zinc(II) porphyrins in A549 cells.