Porphyrin-retinamides: synthesis and cellular studies.
A series of four porphyrin-retinamides containing either all-trans- or 13-cis-retinoid acid residues, directly linked to the para-phenyl position of meso-tetraphenylporphyrin or via a low-molecular-weight PEG spacer, have been synthesized. The biological properties of these conjugates were evaluated in a model cell line, human HEp2, and in neuroblastoma SK-N-DZ cells, which exhibit moderate expression of retinoic acid receptors and retinoic acid-induced differentiation. The directly linked porphyrin-retinamides were taken up by a greater extent (20-50% more) in SK-N-DZ than in HEp2 cells. However, the PEG-containing conjugates accumulated maximally within both cell lines and approximately by the same amount, probably due to their increased amphiphilicity. Among all conjugates, the porphyrin-PEG-13-cis-retinamide accumulated the most in both cell lines (about 5 times more than the non-pegylated conjugates). None of the porphyrin-retinamide conjugates were toxic toward HEp2 cells at concentrations up to 100 microM, and only the hydrophobic non-pegylated conjugates were moderately toxic to SK-N-DZ cells [IC50 (dark) = 56-92 microM, and IC50 (at 1 J/cm2) = 6-8 microM]. All conjugates preferentially localized within cellular vesicles that correlated well to the lysosomes and, in addition, the PEG-containing porphyrin-retinamides were also found in the ER.
Sibrian-Vazquez
Martha
M
Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Jensen
Timothy J
TJ
Vicente
M Graça H
MG
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D008027:Light; D011092:Polyethylene Glycols / Q000737:chemistry; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D005456:Fluorescent Dyes; D011166:Porphyrins; D011092:Polyethylene Glycols; D014212:Tretinoin; C054441:retinamide