Combined arene ruthenium porphyrins as chemotherapeutics and photosensitizers for cancer therapy.

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State: Public
Version: Final published version
Serval ID
serval:BIB_3CF1FFA2E6A5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Combined arene ruthenium porphyrins as chemotherapeutics and photosensitizers for cancer therapy.
Journal
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
Author(s)
Schmitt F., Govindaswamy P., Zava O., Süss-Fink G., Juillerat-Jeanneret L., Therrien B.
ISSN
1432-1327 (Electronic)
ISSN-L
0949-8257
Publication state
Published
Issued date
01/2009
Peer-reviewed
Oui
Volume
14
Number
1
Pages
101-109
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Mononuclear 5-(4-pyridyl)-10,15,20-triphenylporphyrin and 5-(3-pyridyl)-10,15,20-triphenylporphyrin as well as tetranuclear 5,10,15,20-tetra(4-pyridyl)porphyrin (tetra-4-pp) and 5,10,15,20-tetra(3-pyridyl)porphyrin) (tetra-3-pp) arene ruthenium(II) derivatives (arene is C(6)H(5)Me or p-Pr(i)C(6)H(4)Me) were prepared and evaluated as potential dual photosensitizers and chemotherapeutics in human Me300 melanoma cells. In the absence of light, all tetranuclear complexes were cytotoxic (IC(50) < or = 20 microM), while the mononuclear derivatives were not (IC(50) > or = 100 microM). Kinetic studies of tritiated thymidine and tritiated leucine incorporations in cells exposed to a low concentration (5 microM) of tetranuclear p-cymene derivatives demonstrated a rapid inhibition of DNA synthesis, while protein synthesis was inhibited only later, suggesting arene ruthenium-DNA interactions as the initial cytotoxic process. All complexes exhibited phototoxicities toward melanoma cells when exposed to laser light of 652 nm. At low concentration (5 microM), LD(50) of the mononuclear derivatives was between 5 and 10 J/cm(2), while for the tetranuclear derivatives LD(50) was approximately 2.5 J/cm(2) for the [Ru(4)(eta(6)-arene)(4)(tetra-4-pp)Cl(8)] complexes and less than 0.5 J/cm(2) for the [Ru(4)(eta(6)-arene)(4)(tetra-3-pp)Cl(8)] complexes. Examination of cells under a fluorescence microscope revealed the [Ru(4)(eta(6)-arene)(4)(tetra-4-pp)Cl(8)] complexes as cytoplasmic aggregates, whereas the [Ru(4)(eta(6)-arene)(4)(tetra-3-pp)Cl(8)] complexes were homogenously dispersed in the cytoplasm. Thus, these complexes present a dual synergistic effect with good properties of both the arene ruthenium chemotherapeutics and the porphyrin photosensitizer.

Keywords
Antineoplastic Agents/chemical synthesis, Antineoplastic Agents/chemistry, Antineoplastic Agents/therapeutic use, Calixarenes/chemistry, Calixarenes/therapeutic use, Cell Proliferation/drug effects, Cell Proliferation/radiation effects, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Drug Screening Assays, Antitumor, Humans, Light, Metalloporphyrins/chemical synthesis, Metalloporphyrins/chemistry, Metalloporphyrins/therapeutic use, Molecular Structure, Neoplasms/drug therapy, Photosensitizing Agents/chemical synthesis, Photosensitizing Agents/chemistry, Photosensitizing Agents/therapeutic use, Ruthenium/chemistry, Ruthenium/therapeutic use, Time Factors, Tumor Cells, Cultured
Pubmed
Web of science
Create date
13/10/2008 11:52
Last modification date
20/08/2019 14:33
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