Document Detail


In vitro study of the photocytotoxicity of some hypericin analogs on different cell lines.
MedLine Citation:
PMID:  11547550     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study, hypericin analogs with an increased hydrophilic character were synthesized. As chemical modifications alter the lipophilicity/hydrophilicity balance together with the photophysical/chemical background of the molecule the influence of these structural changes on the cellular uptake, retention and subcellular localization in HeLa cells was investigated. Besides, their photocytotoxic effects using three cell lines (HeLa, MCF-7, A431), as well as their plasma protein binding were also assessed. To assess the relative hydrophilic/lipophilic character of hypericin and analogs their retention times were determined on a reversed phase high performance liquid chromatography (C-18) column. The retention time of all the hypericin analogs was < 46 min, except for dibenzyltetramethylhypericin (118 min), while the retention time of hypericin was > 200 min (solvent system: methanol/citrate buffer 30 mM pH 7; 70/30). Hypericin, hexa-, penta- and dibenzyltetramethylhypericin displayed a potent antiproliferative effect at the nanomolar range after photosensitization (3.6 J/cm2). On the contrary, photoactivated tetrasulfonhypericin and fringelite D had no antiproliferative effect on the three cell lines, whereas hypericin polyethylene glycol showed only an intermediate cytotoxic effect on A431 cells. In dark conditions no antiproliferative effect was observed for any photosensitizer. The antiproliferative photo-effect correlated well with the intracellular accumulation as measured using HeLa cells. In general, the photocytotoxic hypericin analogs concentrated to a large extent, while the noncytotoxic compounds were not taken up by the HeLa cells. Furthermore, confocal laser microscopy revealed that all photosensitizers mainly concentrated in the perinuclear region, probably corresponding with Golgi apparatus and the endoplasmic reticulum, except for tetrasulfonhypericin which located at the plasma membrane. In addition, the plasma protein binding studies illustrated that hypericin bind extensively to the low-density lipoproteins, while the other hypericin analogs were mainly bound to heavy proteins (mostly albumin) and to a small extent to low-density lipoproteins.
Authors:
E M Delaey; R Obermuëller; I Zupkó; D De Vos; H Falk; P A de Witte
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Photochemistry and photobiology     Volume:  74     ISSN:  0031-8655     ISO Abbreviation:  Photochem. Photobiol.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-09-07     Completed Date:  2001-10-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376425     Medline TA:  Photochem Photobiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  164-71     Citation Subset:  IM    
Affiliation:
Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, K.U. Leuven, Leuven, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Blood Proteins / metabolism
Chromatography, High Pressure Liquid
Hela Cells
Humans
Perylene / analogs & derivatives*,  chemistry,  pharmacokinetics,  pharmacology*
Photochemistry
Photosensitizing Agents / chemistry,  pharmacokinetics,  pharmacology*
Protein Binding
Structure-Activity Relationship
Subcellular Fractions / metabolism
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Blood Proteins; 0/Photosensitizing Agents; 198-55-0/Perylene; 548-04-9/hypericin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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