title: Far-red-absorbing cationic phthalocyanine photosensitizers: synthesis and evaluation of the photodynamic anticancer activity and the mode of cell death induction.
abstract: Novel zinc, magnesium, and metal-free octasubstituted phthalocyanine photosensitizers bearing [(triethylammonio)ethyl]sulfanyl substituents in the peripheral or nonperipheral positions were synthesized and investigated for their photophysical properties (ΦΔ value up to 0.91, λmax up to 750 nm) and photodynamic anticancer activity. The photodynamic treatment of 3T3, HeLa, SK-MEL-28, and HCT 116 cancer cells revealed that the magnesium complexes were not active (IC50 > 100 μM), whereas the IC50 values of the zinc complexes typically reached values in the submicromolar range with low toxicity in the dark (TC50 ≈ 1500 μM). The subcellular changes upon photodynamic treatment of the HeLa cells indicated that the studied photosensitizers induced damage primarily to the lysosomes, which was followed by a relocalization and damage to other organelles. The time-lapse morphological changes along with the flow cytometry and caspase activity measurements indicated a predominant involvement of necrosis-like cell death.
authors.affiliation: Department of Biochemical Sciences, ‡Department of Pharmaceutical Chemistry and Drug Control, and §Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague , Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
authors.forename: Miloslav
authors.initials: M
authors.lastname: Machacek
authors.forename: Antonin
authors.initials: A
authors.lastname: Cidlina
authors.forename: Veronika
authors.initials: V
authors.lastname: Novakova
authors.forename: Jan
authors.initials: J
authors.lastname: Svec
authors.forename: Emil
authors.initials: E
authors.lastname: Rudolf
authors.forename: Miroslav
authors.initials: M
authors.lastname: Miletin
authors.forename: Radim
authors.initials: R
authors.lastname: Kučera
authors.forename: Tomas
authors.initials: T
authors.lastname: Simunek
authors.forename: Petr
authors.initials: P
authors.lastname: Zimcik
mesh_terms: D016475:3T3 Cells; D065638:Absorption, Radiation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles; D008027:Light; D008274:Magnesium / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D008274:Magnesium; D015032:Zinc; C013647:phthalocyanine