Cellular uptake and photocytotoxicity of glycoconjugated chlorins in HeLa cells

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

“…Purification of the glycochlorins required reverse phase-TLC to give the glycochlorin derivatives in 14-49 % yield. UV-vis spectroscopy of the crude mixture showed for the meta-substituted glycoporphyrins the yield of the bacteriochlorins to be considerably higher than the chlorins unlike the para-substituted derivatives [261] . …”

“…and was optimized to allow functionalization with both protected and deprotected carbohydrates in high yields. A sequential "double-click" process was used to obtain a new class of bismodified 5,10-diglycoporphyrins (263) In continuation of this initial work, a significantly large library of mono-, di-and trideprotected glycoporphyrins (316)(317)(318)(319)(320)(321)(322)(323)(324)(325)(326)(327)(328)(329)(330)(331)261) were synthesized with monosaccharides and for the first time, synthetic disaccharides and trisaccharide [33] . These studies also provide the first examples of bismodified glycosylated porphyrins and a significant highlight was the ligation of the synthetic trisaccharide Lewis X , a histo-blood group antigen.…”

“…However, reduction of the trisubstituted porphyrin yielded two inseparable isomers 2,3-and 7,8-meta-triglucosylated chlorins (516, 517) while the metasubstituted tetraglucosylated chlorin 514f was formed as a mixture of four atropisomers at r.t. [260] . By now, many other glycochlorins have been prepared using the Whitlock method, including a series of 5,10,15,20-tetrakis[3-or 4-(β-D-glycopyranosyloxy)phenyl]chlorins with glucopyranosyl, galactopyranosyl, xylopyranosyl and arabinopyranosyl groups (514a,b,d-i) [261,262] . Note, that reduction can afford a mixture of chlorins and bacteriochlorins which was the case in this study.…”

“…No significant difference in Log P was observed, but chlorins 540a and 540c were only slightly more hydrophilic than 540b,d [271] . Similar methods were used by Hirohara et al to study a range of O-glycosylated tetraarylporphyrins and -chlorins, which showed several advantages including reduced dark cytotoxicity, improved water-solubility, better cellular uptake, and sugar-dependent photocytotoxicity [165,261,262,272,273] . The O-glycosylated chlorins had promising photocytotoxicity in HeLa cells but were difficult to purify.…”

“…Uptake studies in HeLa cells had shown that the chlorins 514a,b,d-i exhibited higher uptake then 639a and either equal or higher uptake then the corresponding porphyrin derivatives [261] . E.g., the 5,10,15,20-tetrakis[3-(β-Dxylopyranosyloxy)phenyl]chlorin 514d showed 50 times higher uptake than 639a and the overall order of uptake was 514d > 514i > 514e > 514a > 514b > 514h > 514f > 514g > 639a.…”