SYNTHESIS OF POSITIVELY CHARGED PHTHALOCYANINES and THEIR ACTIVITY IN THE PHOTODYNAMIC THERAPY OF CANCER CELLS

Abstract

Positively charged zinc containing or metal free phthalocyanines 6a-c and 7a-c were prepared via a three step procedure starting from 4-nitrophthalonitrile. The phthalocyanines contain alkyl chains of different length in order to influence the hydrophilic vs lipophilic character of the compounds. The partition between a hydrophilic (water) and lipophilic (octanol-1) phase was determined, and the photoredox activities were investigated. Initial results on the photodynamic activity of these compounds were compared with those of Dougherty's Photofrin II on different malignant and non-malignant cell lines (XP 29MAmal, CX1, HeLa, S180 and NO17). Positively charged phthalocyanines in vitro showed a higher photodynamic activity than Photofrin II.

Phthalocyanines as Photodynamic Sensitizers*

“…Few positive-charged ZnPC substituted with aliphatic side chain linked to quaternary nitrogen of pyrimidine or other amino groups showed a higher photodynamic activity than HPD when tested in vitro on several cell lines. No significant difference was observed in the uptake of these photosensitizers by malignant and normal cell lines (Wohrle et al, 1990). The substitution with carboxylic groups inactivates, in vitro, ClGaPC (Langlois et al, 1986) and CIAlPC and few recently synthesized amino and hydroxy-alkyl substituted ZnPC did not show improved activity in vitro (Leznoff ef al., 1989).…”

Ionic Interactions between Charged Phthalocyanine and Fullerene Derivatives

“…Symmetrically substituted phthalocyanines 1-3 were prepared as described before. [16,17] Fullerene derivatives 8 [18,19] and 9 [20] were prepared after known procedures. Analytical reagent grade (Sigma-Aldrich) lithium metal, zinc acetate dihydrate, iodomethane, acetic acid, 2-mercaptoethanol and borate buffer solution were used as purchased.…”

“…[16] The positively charged phthalocyanines 2,3 could be obtained by the reaction of pyridyloxy-substituted phthalonitriles with a zinc salt followed by alkylation with methyl iodide [17] .…”

Thermodynamic and spectroscopic study on the binding of interaction anionic phthalocyanine with calf thymus DNA

“…A long triplet lifetime and a relatively high triplet quantum yield, which are useful qualities for a photosensitizer, characterize metallophthalocyanines containing diamagnetic metal ions such as Al +3 and Zn +2 [16]. Positively charged phthalocyanines possess promising photosensitizing properties for the photodynamic therapy of cancer, showing a higher photodynamic activity in vitro than the commonly used haematoporphyrin [29]. It has been observed that the uptake and the killing of cells are higher for positively charged sensitizers than for neutral or negatively charged ones [30].…”