Synthesis of Water-Soluble Thioglycosylated trans -A 2 B 2 Type Porphyrins: Cellular Uptake Studies and Photodynamic Efficiency

• Published in: Journal of organic chemistry 2020-05, Vol.85 (10), p.6309-6322
• Main Authors: Pandey, Vijayalakshmi, Raza, Md Kausar, Joshi, Pooja, Gupta, Iti
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b03491

The synthesis of water-soluble thioglycosylated A B type porphyrins and their zinc(II) complexes is reported. The water-soluble -A B porphyrins were synthesized in two steps, via [2+2] condensation between thioglycosylated dipyrromethanes and aromatic aldehydes in 15-21% yields. The thioglycosylated -A B porphyrins showed decent singlet oxygen generation, which was supported by the intracellular DCFDA study. The cellular investigations of thioglycosylated A B 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 IC values between 23.3 and 44.2 μM in the dark, whereas, after visible light exposure, the photosensitizers exhibited IC values around 11.1-23.8 μM. The water-soluble thioglycosylated zinc(II) porphyrins having two -butylcarbazole groups exhibited an excellent degree of photocytotoxicity (IC = 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.