title: Novel amphiphilic cationic porphyrin and its Ag(II) complex as potential anticancer agents.
abstract: 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), (1)H 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.
authors.affiliation: Department of Chemistry, Pharmacy Faculty, Yerevan State Medical University, 2 Koryun Str., Yerevan 0025, Armenia. Electronic address: artak.tovmasyan@duke.edu.
authors.forename: Artak
authors.initials: A
authors.lastname: Tovmasyan
authors.affiliation: Department of Genetics and Cytology, Yerevan State University, 1 Alex Manoogian Str., Yerevan 0025, Armenia; Institute of Molecular Biology, NAS RA, 7 Hasratyan Str., Yerevan 0014, Armenia.
authors.forename: Nelli
authors.initials: N
authors.lastname: Babayan
authors.affiliation: Institute of Molecular Biology, NAS RA, 7 Hasratyan Str., Yerevan 0014, Armenia.
authors.forename: David
authors.initials: D
authors.lastname: Poghosyan
authors.affiliation: Department of Genetics and Cytology, Yerevan State University, 1 Alex Manoogian Str., Yerevan 0025, Armenia.
authors.forename: Kristine
authors.initials: K
authors.lastname: Margaryan
authors.affiliation: Department of Chemistry, Pharmacy Faculty, Yerevan State Medical University, 2 Koryun Str., Yerevan 0025, Armenia.
authors.forename: Boris
authors.initials: B
authors.lastname: Harutyunyan
authors.affiliation: Institute of Molecular Biology, NAS RA, 7 Hasratyan Str., Yerevan 0014, Armenia.
authors.forename: Rusanna
authors.initials: R
authors.lastname: Grigoryan
authors.affiliation: Institute of Molecular Biology, NAS RA, 7 Hasratyan Str., Yerevan 0014, Armenia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Sarkisyan
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevic
authors.affiliation: Molecular Structure Research Center, NAS RA, 26 Azatutian Str., Yerevan 0014, Armenia.
authors.forename: Suren
authors.initials: S
authors.lastname: Mamyan
authors.affiliation: Department of Chemistry, Pharmacy Faculty, Yerevan State Medical University, 2 Koryun Str., Yerevan 0025, Armenia.
authors.forename: Lida
authors.initials: L
authors.lastname: Sahakyan
authors.affiliation: Department of Genetics and Cytology, Yerevan State University, 1 Alex Manoogian Str., Yerevan 0025, Armenia.
authors.forename: Rouben
authors.initials: R
authors.lastname: Aroutiounian
authors.affiliation: Department of Chemistry, Pharmacy Faculty, Yerevan State Medical University, 2 Koryun Str., Yerevan 0025, Armenia. Electronic address: ghrob@mail.ru.
authors.forename: Robert
authors.initials: R
authors.lastname: Ghazaryan
authors.affiliation: Department of Genetics and Cytology, Yerevan State University, 1 Alex Manoogian Str., Yerevan 0025, Armenia; Institute of Molecular Biology, NAS RA, 7 Hasratyan Str., Yerevan 0014, Armenia.
authors.forename: Gennadi
authors.initials: G
authors.lastname: Gasparyan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011166:Porphyrins / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D012834:Silver / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D011166:Porphyrins; D012834:Silver
keywords: Ag porphyrin; Amphiphilic porphyrin; Anticancer activity; Cytotoxicity; Genotoxicity; Photosensitizer
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