Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 17. Photosensitizing properties and cellular effects of ZnIIoctacationic and ZnII/PtIIhexacationic macrocycles in aqueous media: Perspectives of multimodal anticancer potentialities.
The photosensitizing activity of two multiply charged porphyrazine derivatives, i.e. the ZnIIspecies [(CH3)8LZn]8+and the ZnII/PtIIheterobimetallic complex [(PtCl2)(CH3)6LZn]6+(neutralized byI-ions; L=tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazinato dianion) has been examined in the water medium in the presence of SDS under experimental conditions in which the two species are present exclusively in their monomeric form. The determined quantum yield values (ΦΔ) for both complexes, of interest in photodynamic therapy (PDT), are 2.3-2.5 higher than that of the aluminium compound PcAlSmix(Photosens®) used as the reference standard, an encouraging result for the application of the two cationic species as anticancer curative drugs in PDT. Investigation was also extended to explore the cellular effects on the melanoma C8161 and the oral squamous carcinoma CA-1 cell lines like viability, cellular uptake, cell death modality and cell cycle distribution experiments. The IC50values for the ZnIIand ZnII/PtIIcations are consistently lower than those of the reference standard, thus the degree of efficiency as anticancer agents being in the order octacation≫hexacation>PcAlSmix. A large prevalence of apoptosis with respect to necrosis is observed for both charged complexes. Thus, all achieved information from photoactivity and in vitro tests in water solution further enhance perspectives for the application of the two ZnIIcation [(CH3)8LZn]8+and the related ZnII/PtIIanalog [(PtCl2)(CH3)6LZn]6+as potential bi-multimodal anticancer drugs.
Dipartimento di Chimica, Università Sapienza, P.le A. Moro 5, 00185 Roma, Italy. Electronic address: elisa.viola@uniroma1.it.
Elisa
E
Viola
Dipartimento di Chimica, Università Sapienza, P.le A. Moro 5, 00185 Roma, Italy. Electronic address: mariapia.donzello@uniroma1.it.
Maria Pia
MP
Donzello
Dipartimento di Chimica, Università Sapienza, P.le A. Moro 5, 00185 Roma, Italy.
Fabiola
F
Sciscione
Centre for Cutaneous Research, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
Kous
K
Shah
Dipartimento di Chimica, Università Sapienza, P.le A. Moro 5, 00185 Roma, Italy.
Claudio
C
Ercolani
Centre for Cutaneous Research, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK. Electronic address: g.trigiante@qmul.ac.uk.
Giuseppe
G
Trigiante
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D047028:Macrocyclic Compounds; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry*; D011719:Pyrazines; D011725:Pyridines / Q000737:chemistry; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D047028:Macrocyclic Compounds; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; D011719:Pyrazines; D011725:Pyridines; D015032:Zinc
Anticancer photodynamic therapy; Antitumoral in vitro tests; Photosensitizers; Pyrazinoporphyrazine macrocycles