Novel amphiphilic cationic porphyrin and its Ag(II) complex as potential anticancer agents

In the present study we have synthesized a novel amphiphilic porphyrin and its Ag(II) complex through modification of water-soluble porphyrinic structure in order to increase its lipophilicity and in turn pharmacological potency. New cationic non-symmetrical meso-substituted porphyrins were characte...

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Bibliographic Details
Published in:Journal of inorganic biochemistry Vol. 140; pp. 94 - 103
Main Authors: Tovmasyan, Artak, Babayan, Nelli, Poghosyan, David, Margaryan, Kristine, Harutyunyan, Boris, Grigoryan, Rusanna, Sarkisyan, Natalia, Spasojevic, Ivan, Mamyan, Suren, Sahakyan, Lida, Aroutiounian, Rouben, Ghazaryan, Robert, Gasparyan, Gennadi
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01.11.2014
Subjects:
Ag porphyrin
Amphiphilic porphyrin
Anticancer activity
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cations
Cell Line, Tumor
Cytotoxicity
Drug Screening Assays, Antitumor
Genotoxicity
Humans
Photosensitizer
Porphyrins - chemistry
Proton Magnetic Resonance Spectroscopy
Silver - chemistry
Spectrometry, Mass, Electrospray Ionization
Amphiphilic porphyrin
KKSFBLOIWJHIPV-UHFFFAOYSA-N
Anticancer activity
Genotoxicity
Ag porphyrin
Cytotoxicity
IAMUUOQNJVLXHZ-HUFLXKANSA-L
Photosensitizer
MPCLPUHHGBHJOC-VDCLEYLXSA-N
ISSN:0162-0134, 1873-3344, 1873-3344
Online Access:Get full text
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Summary:In the present study we have synthesized a novel amphiphilic porphyrin and its Ag(II) complex through modification of water-soluble porphyrinic structure in order to increase its lipophilicity and in turn pharmacological potency. New cationic non-symmetrical meso-substituted porphyrins were characterized by UV–visible, electrospray ionization mass spectrometry (ESI-MS), 1H NMR techniques, lipophilicity (thin-layer chromatographic retention factor, Rf), and elemental analysis. The key toxicological profile (i.e. cytotoxicity and cell line- (cancer type-) specificity; genotoxicity; cell cycle effects) of amphiphilic Ag porphyrin was studied in human normal and cancer cell lines of various tissue origins and compared with its water-soluble analog. Structural modification of the molecule from water-soluble to amphiphilic resulted in a certain increase in the cytotoxicity and a decrease in cell line-specificity. Importantly, Ag(II) porphyrin showed less toxicity to normal cells and greater toxicity to their cancerous counterparts as compared to cisplatin. The amphiphilic complex was also not genotoxic and demonstrated a slight cytostatic effect via the cell cycle delay due to the prolongation of S-phase. As expected, the performed structural modification affected also the photocytotoxic activity of metal-free amphiphilic porphyrin. The ligand tested on cancer cell line revealed a dramatic (more than 70-fold) amplification of its phototoxic activity as compared to its water-soluble tetracationic metal-free analog. The compound combines low dark cytotoxicity with 5 fold stronger phototoxicity relative to Chlorin e6 and could be considered as a potential photosensitizer for further development in photodynamic therapy. The cytotoxicity of amphiphilic Ag(II) porphyrin on various cancer and normal cells is presented and compared to that of cisplatin. [Display omitted]
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ISSN:0162-0134
1873-3344
1873-3344
DOI:10.1016/j.jinorgbio.2014.06.013