Photodynamic properties of naphthosulfobenzoporphyrazines, novel asymmetric, amphiphilic phthalocyanine derivatives

Margaron, Philippe; Langlois, Réjean; Lier, Johan E. van; Gaspard, S.

doi:10.1016/1011-1344(92)85097-e

Cited by 43 publications

(23 citation statements)

References 16 publications

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“…Although the V-79 cells are nonmalignant, they are immortal, which accounts for their proliferative behaviour being similar to that of malignant cells [19]. In agreement with other authors [20,21], V-79 cells were found to be a suitable biological model system for the in vitro studies. Both cell lines are appropriate for PDT studies.…”

Section: Discussionsupporting

confidence: 76%

In vitro effects and localisation of the photosensitizers m-THPC and m-THPC MD on carcinoma cells of the human breast (MCF-7) and chinese hamster fibroblasts (V-79)

et al. 1997

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Section: Discussionsupporting

confidence: 76%

In vitro effects and localisation of the photosensitizers m-THPC and m-THPC MD on carcinoma cells of the human breast (MCF-7) and chinese hamster fibroblasts (V-79)

et al. 1997

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“…Simple procedures to prepare AlPcS enriched in the active disulphonated derivatives have been reported Ambroz et al, 1991) and their in vivo pattern of photosensitisation have been studied in detail (Nuutinen et al, 1991;Loh et al, 1992). Addition of hydrophobic tertiary butyl (Paquette et al, 1991), phthalimidomethyl (Boyle et al, 1992) or benzene groups (Margaron et al, 1992) on the non-substituted, adjacent benzo rings of disulphonated Pc's further enhances the amphiphilic properties of these drugs resulting in increased potential for direct cell killing during PDT. Differently sulphonated tetraphenylporphins follow similar biodistribution pattern as the analogous sulphophthalocyanines, with the derivative featuring two adjacent sulfonates showing the highest photocytotoxicity (Kessel et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Biological activities of phthalocyanines – XVI. Tetrahydroxy- and tetraalkylhydroxy zinc phthalocyanines. Effect of alkyl chain length on in vitro and in vivo photodynamic activities

Boyle

Leznoff²,

Lier³

1993

Br J Cancer

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Summary Zinc phthalocyanine substituted with four hydroxyl groups attached to the macrocycle, either directly or via spacer chains of three or six carbon atoms, were tested for their photodynamic ability to inactivate Chinese hamster lung fibroblasts (line V-79) in vitro, and to induce regression of EMT-6 tumours grown subcutaneously in Balb/c mice. Their potential to inflict direct cell killing during photodynamic therapy was investigated by examining vascular stasis immediately following photoirradiation using fluorescein as a marker, and also by an in vivo/in vitro EMT-6 cell survival assay. Both of the tetraalkylhydroxy substituted zinc phthalocyanines are effective photodynamic sensitisers in vivo with the tetrapropylhydroxy compound exhibiting about twice the activity of the tetrahexylhydroxy analogue. The differences in activities were accentuated in vitro, the tetrapropylhydroxy compound was two orders of magnitude more potent than the tetrahexylhydroxy analogue in photoinactivating V-79 The photosensitiser currently used, Photofrin II.m (P-II), is a complex mixture of porphyrin dimers and oligomers, the active component of which, as yet, remains unidentified. It is, therefore, of increasing importance that 'second generation' photosensitisers of known composition and increased photodynamic activity are developed to provide an alternative to P-II. Phthalocyanines (Pc's) have been proposed as promising potential PDT agents (for recent reviews see van Rosenthal, 1991) primarily because of the high molar absorptivity of these compounds in the red region of the visible spectrum (et105 M' cm' at 670-680 nm when fully monomerised compared to a103M-'cm'1 at 630nm for P-II) where tissue transmission by visible light is more efficent. Their photodynamic activities in vivo largely depend on pharmacokinetics and intratissular distribution pattern and only limited structure-activity relationships have been put forth (Paquette & van Lier, 1992). Degree of sulfonation of Pc's is the most studied structural variable, however, many alternative substituents are possible and remain unexplored. An approach towards the synthesis of novel Pc's on the basis of known structural data, and good photodynamic properties of related compounds, could be potentially rewarding, and this is the rationale for the current study.Berenbaum et al. (1986) tested the ortho, meta and para isomers of meso-tetra(hydroxyphenyl)porphine (THPP) for their in vivo photodynamic activity and skin photosensitisation. Although the m-and o-THPP have very similar photophysical properties and similar absorbances at the wavelength used for PDT (Bonnett et al., 1988), the m-THPP is twice as effective as o-THPP in sensitising tumours, while o-THPP is four times as potent as m-THPP in sensitising skin. Doses of p-THPP and m-THPP that produce equal tumour necrosis are of the ratio 5:1, while their molar absorbances at the illuminating wavelengths are of the ratio 2:1. These data suggest that m-THPP has considerably greater ability than the para and ortho iso...

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“…It is emphasised that 2d exhibited excellent photoantimicrobial activity, given the similar high efficacy exhibited against the yeast challenge. In terms of the ionisation pattern discussed above, compound 2d, being potentially tricationic (Figure 2), exhibits one which has been shown to be active by several groups [19,20]. Thus the molecule has recognisable lipophilic and hydrophilic regions which may aid in orientation in membranous regions in the microbial cell.…”

Section: Photosensitisersmentioning

confidence: 99%

“…The phenothiazinium salt methylene blue ( Figure 1) has considerable antiquity among dyes used in biology and medicine, having featured in the vanguard of colorants for microscopy in the late 19 th Century. It was also a lead compound in the work of Koch, Ehrlich and others in their development of the theory of selective toxicity and, subsequently, of modern chemotherapy [1].…”

Section: Introductionmentioning

confidence: 99%

Phenothiazinium photoantimicrobials with basic side chains

Wainwright

Antczak

Bača

et al. 2015

Journal of Photochemistry and Photobiology B: Biology

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Derivatives of the standard cationic photosensitiser, methylene blue, were synthesised, having extra amino (basic) functionality in the auxochromic side-chain. The resulting analogues were profiled for photodynamic activity in vitro, and screened against standard Gram-positive and Gram-negative bacteria for photobactericidal activity. The substitution pattern of the derivatives was such that ionisation of the amino groups in situ, via protonation, provided a range of charge distribution and degree of charge across the molecular framework. While most examples exhibited greater activity than the lead compound, in addition to similar activity to the known, but more powerful, phenothiazinium photoantimicrobial, dimethyl methylene blue, this was also associated with relatively high dark toxicity, inferring that these compounds were targeting crucial structures before illumination. One derivative having an asymmetrical structure, with separation between a lipophilic and a hydrophilic region exhibited a combination of very high phototoxicity coupled with very low dark effects, against both the standard screen and an additional one containing further, relevant pathogen species, including Candida albicans. It is suggested that the great activity of this analogue is due to efficient membrane targeting.Running header: Basic Phenothiazinium Derivatives

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Photodynamic properties of naphthosulfobenzoporphyrazines, novel asymmetric, amphiphilic phthalocyanine derivatives

Cited by 43 publications

References 16 publications

In vitro effects and localisation of the photosensitizers m-THPC and m-THPC MD on carcinoma cells of the human breast (MCF-7) and chinese hamster fibroblasts (V-79)

In vitro effects and localisation of the photosensitizers m-THPC and m-THPC MD on carcinoma cells of the human breast (MCF-7) and chinese hamster fibroblasts (V-79)

Biological activities of phthalocyanines – XVI. Tetrahydroxy- and tetraalkylhydroxy zinc phthalocyanines. Effect of alkyl chain length on in vitro and in vivo photodynamic activities

Phenothiazinium photoantimicrobials with basic side chains

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