Phthalocyanines and Tetrapyrazinoporphyrazines with Two Cationic Donuts: High Photodynamic Activity as a Result of Rigid Spatial Arrangement of Peripheral Substituents

Abstract

High photodynamic activity was observed for hexadeca-cationic zinc, magnesium, and metal-free phthalocyanines (Pcs) and tetrapyrazinoporphyrazines with EC values as low as 5 nM (MCF-7 cells) for the best compound; this activity was several times better than that of clinically established photosensitizers verteporfin, temoporfin, SAlOHPc, or protoporphyrin IX. This lead compound was characterized by low dark toxicity (TC = 369 μM), high efficiency against other cell lines (HCT 116 and HeLa), and possible activation by light above 680 nm. The excellent photodynamic activity resulted from the rigid spatial arrangement of the quaternized triazole moieties above and below the Pc core, as confirmed by X-ray crystallography. The triazole moieties thus formed two "cationic donuts" that protected the hydrophobic core against aggregation in water. The lysosomes were found to be the site of subcellular localization and were consequently the primary targets of photodynamic injury, resulting in predominantly necrotic cell death.

Synthesis, Characterization and Photodynamic Activity against Bladder Cancer Cells of Novel Triazole-Porphyrin Derivatives

“…These compounds are considered to be highly relevant in the medicinal field due to their high ability to act as photosensitizers in photodynamic therapy (PDT) [4]. In fact, porphyrins and analogues are special candidates for the management of oncological diseases by following the PDT therapy [5][6][7][8][9][10][11][12][13]. PDT is centered in a photooxidation process occurring in target tissues through three key components: photosensitizer (PS), oxygen, and light (sources emitting within the absorption spectrum of the PS) [14].…”

Highly Efficient Water-Soluble Photosensitizer Based on Chlorin: Synthesis, Characterization, and Evaluation for Photodynamic Therapy

“…Given the short half-life of 1 O 2 , the intracellular localization of a PS determines the efficiency of photoinduced cell death and the primary target of photodamage. , The subcellular location, efficacy, and mechanism of cell death induced by a PS depends on its charge, amphiphilicity, and partition coefficients . Cellular uptake and intracellular distribution of HPS were evaluated by confocal laser scanning microscopy (CLSM).…”

Biotinylated-cationic zinc(II) phthalocyanine towards photodynamic therapy

“…Asymmetrical A3Btype zinc(II) phthalocyanine (ZnI) was prepared according to the procedure earlier reported by our group using a 4:1 ratio mixture of bis{2,6bis[(1H 1,2,4triazol1yl)methyl]4methylphenoxy}phthaloni trile [43,44] and 4iodophthalonitrile through statistical condensation in dimethylaminoethanol (DMAE) in the presence of anhydrous zinc(II) chloride as the metal source under nitrogen atmosphere at 140 °C [45]. The ZnI was then decorated with biotin via the Pd(0)catalyzed Sonogashira coupling reaction in the presence of bicatalytic systems (PdCl 2 (PPh 3 ) 2 /CuI) and triethylamine (TEA) at room temperature for 24 h. Treatment of this novel biotinylatedzinc(II) phthalocyanine (Pc-1) with dimethyl sulphate in dimethylformamide (DMF) at 120 °C produced the quaternized watersoluble macrocyclic analogue Pc-2 (Scheme 1).…”

“…Such triazolyl activation improved the macrocyclic potential toward HeLa cells (EC 50 = 12 nM, l > 570 nm, 11.2 J . cm 2 ) with low dark toxicity (TC 50 = 369 mM) [43]. Considering this outstanding PDT efficacy, we attempted to design a novel A3B asymmetrical Pcs bearing six bulky phenoxyl bis(triazolyl) moieties and one biotin group.…”