Morphological aspects of an experimental tumour photosensitized with a meso-substituted cationic porphyrin

Villanueva, Ángeles; Caggiari, Laura; Jori, Giulio; Milanesi, Carla

doi:10.1016/1011-1344(93)06982-9

Cited by 69 publications

(37 citation statements)

References 9 publications

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“…Unfortunately, the ortho hydroxy phenyl isomer causes skin sensitivity, but the meta and para isomers show improved tumor phototoxicity and selectivity over haematoporphryin derivative [33,65]. The methyl pyridinium salt causes significant tumor photodamage, attributed to the increase in hydrophilicity imparted by the cationic substituent [66]. A series of asymmetric amide protoporphyrin derivatives studied by Haylett et al [67] was found to be efficient sensitizers of singlet oxygen with quantum yields of 0.01 Á/0.64.…”

Section: Porphryinsmentioning

confidence: 99%

Photosensitized singlet oxygen and its applications

DeRosa

2002

Coordination Chemistry Reviews

2,614

2,134

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Section: Porphryinsmentioning

confidence: 99%

Photosensitized singlet oxygen and its applications

DeRosa

2002

Coordination Chemistry Reviews

2,614

2,134

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“…Several have clinical potential as anticancer agents in photodynamic therapy (3,4), probably as a consequence of their ability to selectively accumulate on the surface of tumor cells, become internalized, bind to genomic DNA, and then induce DNA strand cleavage. One such compound is tetra-(N-methylpyridyl) porphyrin (TMPy: Fig.…”

mentioning

confidence: 99%

A DNA–porphyrin minor-groove complex at atomic resolution: The structural consequences of porphyrin ruffling

Bennett

Krah

Wien

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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The crystal structure of a B-type DNA hexanucleotide duplex complexed with the porphyrin molecule nickel-[tetra-N-methylpyridyl] porphyrin has been solved by multiwavelength anomalous diffraction phasing and refined to an R factor of 11.5% at a resolution of 0.9 Å. The structure has been solved and refined as two crystallographically independent duplexes, stacked end to end. Contrary to expectation, the porphyrin molecule is not intercalated into the duplex but is stacked onto the ends of the two-duplex stack. The porphyrin molecule is highly buckled as a consequence of the nickel coordination, which produces large changes in local DNA structure. A second mode of porphyrin binding is apparent as a consequence of crystal packing, which places the ligand in the minor groove of an adjacent duplex. This structure thus provides, to our knowledge, the first atomic visualization of minor-groove binding for a porphyrin molecule. The geometry of groove binding provides a ready explanation for porphyrin-induced DNA strand cleavage at deoxyribose residues.DNA structure ͉ minor groove binding ͉ end capping T he interactions of cationic porphyrins with nucleic acids have received considerable attention (1, 2). Several have clinical potential as anticancer agents in photodynamic therapy (3, 4), probably as a consequence of their ability to selectively accumulate on the surface of tumor cells, become internalized, bind to genomic DNA, and then induce DNA strand cleavage. One such compound is tetra-(N-methylpyridyl) porphyrin (TMPy: Fig. 1a), which can be coordinated with a range of transition metals (1, 2, 5, 6). TMPy has more direct antitumor activity, possibly as a consequence of its ability to inhibit the telomerase enzyme (7). Binding to quadruplex DNA as well as to duplexes has been reported for TMPy and various complexes (8-10). Stabilization of G-quadruplex structures has been shown to be the mechanism whereby TMPy inhibits telomerase from catalyzing the synthesis of further linear telomere repeats. NMR and photocleavage data have been interpreted in favor of a model with a TMPy molecule externally stacking onto guaninequadruplex structures (8-10).Noncovalent interactions of TMPy and its metal complexes with duplex DNA are sequence dependent (2, 11), with intercalation occurring at 5Ј-CpG sites, as shown by NMR and other biophysical studies (12, 13) as well as molecular modeling (13,14). A crystallographic analysis (15) of the Cu 2ϩ complex of TMPy bound to the sequence 5Ј-d(CGTACG) 2 also found the ligand intercalated at this site, but with the 5Ј-end cytosine swung out in an extrahelical arrangement. By contrast, biophysical and modeling (14, 16) studies have suggested that TMPy itself (and many of its metal complexes) bind in the minor groove at A͞T sequences and perturb the double helix only to a minimal extent at such sites (16). No structural data has been reported to date on groove-binding modes. TMPy itself is a planar molecule (14, 15), and it has been assumed that the groove binding would therefore be analogou...

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“…First-generation photosensitisers were haematoporphyrin derivatives (HPD) [1][2][3][4][5], of which the most used mixture is Photofrin II [6].…”

Section: Introductionmentioning

confidence: 99%

Photodynamically Induced Changes of Acetylcholinesterase Activity From Human Erythrocytes

2001

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The light and photodynamic actions on acetylcholinesterase activity from human erythrocytes were studied. After light irradiation (670 nm, semiconducting low power laser) the maximum reaction rate increased from 13.3 to 14.8 mumol per ml packed cells per min for an energy dose 9 J, and above that dose it decreased (10.8 mumol per ml packed cells per min for an energy dose of 15 J). The Michaelis-Menten constant changed in the opposite direction. After irradiation of erythrocyte suspension in the presence of zinc phthalocyanine the reaction rate increased, reaching the maximum for energy dose of 0.75 J (16.85 in comparison to the control value of 14.7 mumol per ml packed cells per min. Similarly, the Michaelis-Menten constant decreased reaching a minimum for an energy dose of 0.75 J (0.04 mM compared to 0.07 mM for control). Incubation of erythrocytes with the dye in the dark increased the reaction rate from 13.3 to 14.7 mumol per ml packed cells per min. Neither the incubation in the dark nor irradiation with laser light caused changes of enzyme activity in the presence of chloroaluminium or metal-free phthalocyanine.

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Morphological aspects of an experimental tumour photosensitized with a meso-substituted cationic porphyrin

Cited by 69 publications

References 9 publications

Photosensitized singlet oxygen and its applications

Photosensitized singlet oxygen and its applications

A DNA–porphyrin minor-groove complex at atomic resolution: The structural consequences of porphyrin ruffling

Photodynamically Induced Changes of Acetylcholinesterase Activity From Human Erythrocytes

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