Synthesis and biological evaluation of thioglycosylated porphyrins for an application in photodynamic therapy

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

“…Quantitative deacetylation gave 447-449. Similarly, a range of meso-aryl porphyrins and protoporphyrin IX derivatives appended with deprotected S-glucose, mannose and galactose residues were synthesized [199] . Series one was synthesized from preformed ortho-and para-hydroxylphenyl precursors (213, 214) using Little conditions, to yield 223 and 224 in 91 % and 84 % yields when reacted with 1,3,dibromopropane and subsequently underwent glycosylation with 2,3,4,6-tetra…”

“…This was followed by full deprotection (456a-458a) and partial deprotection (456b-458b) in quantitative yields. The relative stability of β-thioglucosides versus β-glucosides towards hydrolysis was tested by β-glucosidases finding β-thioglucoside to be a more stable residue [199] . 5,10,15,20-Tetra(pentafluorophenyl)porphyrin (TPPF 20 ) is a useful porphyrin precursor as the p-position of the pentafluorophenyl residue is susceptible to nucleophilic substitution.…”

“…For example, Drain et al synthesized nonhydrolyzable tetrasubstituted glycoporphyrins (e.g., 87, 95) in high yields from TPPF 20 in a nucleophilic substitution reaction with thio-glucose and thio-galactose derivatives to decrease the acid hydrolysis of the glycosyl bond using C-or S-glycoside linkages to reduce drug dosage requirements [172,247] . S-or C-glycoside type PSs were previously synthesized in relatively low yields [171,199,218,243] . However, significantly higher yields > 85 % were observed with both the acetyl protected or the free hydroxyl sugar present with such an approach [172,247] .…”

“…Although Hp and similar systems have often been used for comparison in the studies outlined here only one paper appears to have directly compared meso and β-substituted glycoporphyrins. Sylvain et al determined the photocytotoxicities of two compound series (231-236 and 456b-458b) against K562 chronic leukaemia cells with Photofrin ® as a reference [199] . The compounds required 24 h post-treatment incubation in the dark at 37 °C and only with irradiation times of > 60 minutes were they comparable to Photofrin ® .…”

“…All the thioglycosylated mesoaryl porphyrins ortho isomers (231, 233, 235) and only the glucose para isomer 234 were found to be photocytotoxic. The partially deprotected isohematoporphyrin derivatives (456b-458b) were also found to be photocytotoxic and were more efficient then Photofrin ® indicating that their PDT effect is dependent upon their amphiphilicity rather than the glycosyl moiety [199] . One of the first few examples of sugar-containing phthalocyanines tested for their photoactivity were 617 and 618a-c which were studied on HepG2 human hepatocarcinoma cells [317] .…”