Synthesis, cellular internalization and photodynamic activity of glucoconjugated derivatives of tri and tetra(meta-hydroxyphenyl)chlorins

Laville, Isabelle; Figueiredo, Tamiris Vilas Boas; Loock, Bernard; Pigaglio, Sophie; Maillard, Ph.; Grierson, David S.; Carrez, Danièle; Croisy, Alain; Blais, J.

doi:10.1016/s0968-0896(03)00050-6

Cited by 119 publications

(93 citation statements)

References 37 publications

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“…However, these cell testing results suggest that the nucleophilic substitution with amines and alcohols on PFP-substituted compounds can be used to fine-tune the properties of porphyrins towards a higher amphiphilicity and membrane affinity. [7,52] Currently, further substitution patterns on the porphyrins are investigated to increase this membrane affinity. …”

Section: Cell Testingmentioning

confidence: 99%

Nucleophilic Aromatic Substitution on Pentafluorophenyl‐Substituted Dipyrranes and Tetrapyrroles as a Route to Multifunctionalized Chromophores for Potential Application in Photodynamic Therapy

Gutsche

Ortwerth

Gräfe

et al. 2016

Chemistry A European J

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Abstract:The application of porphyrinoids in biomedical fields like photodynamic therapy (PDT) requires the introduction of functional groups to adjust their solubility in the biological environment and to allow a coupling to other active moieties or carrier systems. A valuable motif in this regard is the pentafluorophenyl (PFP)-substituent, as the PFP-group easily undergoes a regiospecific nucleophilic replacement (S N Ar) of the para-fluorine atom by a number of nucleophiles. Here, it is shown that -alternatively to an amino-substitution on the final porphyrinoid or BODIPY -the precursor 5-(PFP)-dipyrrane can be modified with amines (or alcohols). These dipyrranes were transformed into amino-substituted BODIPYs. Condensation of these dipyrranes with aldehydes gives access to trans-A 2 B 2 -porphyrins and -A 2 B-corroles. Using pentafluorobenzaldehyde another para-fluorine atom can be introduced enabling the synthesis of multifunctionalized tetrapyrroles. Furthermore, alkoxy-and amino-substituted dipyrranes were applied to the synthesis of A 3 B 3 -hexaphyrins. With this approach polar porphyrins can be prepared, which exhibit in vitro PDT activity against several tumor cell lines.

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Section: Cell Testingmentioning

confidence: 99%

Nucleophilic Aromatic Substitution on Pentafluorophenyl‐Substituted Dipyrranes and Tetrapyrroles as a Route to Multifunctionalized Chromophores for Potential Application in Photodynamic Therapy

Gutsche

Ortwerth

Gräfe

et al. 2016

Chemistry A European J

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“…Similar mTHPC glycoconjugates were prepared as illustrated in Scheme 24. However, reduction of the trisubstituted porphyrin yielded two inseparable isomers 2,3-and 7,8-meta-triglucosylated chlorins (516, 517) while the metasubstituted tetraglucosylated chlorin 514f was formed as a mixture of four atropisomers at r.t. [260] . By now, many other glycochlorins have been prepared using the Whitlock method, including a series of 5,10,15,20-tetrakis[3-or 4-(β-D-glycopyranosyloxy)phenyl]chlorins with glucopyranosyl, galactopyranosyl, xylopyranosyl and arabinopyranosyl groups (514a,b,d-i) [261,262] .…”

Section: Reductionmentioning

confidence: 99%

“…This suggests the sugar dependence of PDT activity could be due to interactions between glycoporphyrins and endogenous biomolecules such as albumin. Glycochlorin interactions with serum albumin had previously been shown to affect cellular uptake in HT29 cells [260] . The interaction between the glycoporphyrins and BSA was evaluated by electronic absorption, fluorometric and circular dichroic titrations [272] .…”

Section: Meso-substituted Porphyrinsmentioning

confidence: 99%

“…Surprisingly, the cellular uptake of 516, 517 was 30 % lower than mTHPC and exhibited saturation. This increase in toxicity was due to the higher accumulation in mitochrondria, approximately a 2-fold increase in mitochondrial affinity for the glycoconjugated derivative 516, 517 [260] . Next to the basic PDT activity the metabolism of the PS must be considered as well.…”

Section: Hydroporphyrinsmentioning

confidence: 99%

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Chemical Synthesis and Medicinal Applications of Glycoporphyrins

Moylan¹,

Scanlan²,

Senge

2015

CMC

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Abstract:This review presents an in-depth overview of the modification of porphyrins with bioconjugates and their applications in medicine today. Porphyrin bioconjugates ranging from nucleotides to steroids are under active scrutiny. However, carbohydrates have been at the forefront of such research in recent years and offer significant potential. This is attributed to their own selectivity to lectins on the surface of cancer cells and their influence on the amphiphilicity of the porphyrin macrocycle. These characteristics and the tendency of porphyrin photosensitizers to accumulate in tumor tissues make glycoporphyrins promising candidates for use as photosensitizers. Thus, a detailed overview of the synthesis and biological evaluation of glycoporphyrins is given with a particular focus on their applications in photodynamic therapy and their future prospects as drug candidates have been reported.

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“…This often requires significant chemical manipulation [6] (more synthetic steps) or complex formulation strategies [9,10] (liposomes, nanomaterials) whereby the biocompatibility is somewhat unclear. Current bioconjugate research developments [11,12,13,14] (antibodies, sugars, steroids, etc.) involve expensive and complicated methodology, whilst state-of-the-art drugs such as Temoporfin are undergoing further developments [15,16], mostly in terms of nanoformulations to increase their efficacy and application potential or in terms of new uses, e.g., antimicrobial action [17].…”

Section: Introductionmentioning

confidence: 99%

Lead structures for applications in photodynamic therapy. 5. Synthesis and biological evaluation of water soluble phosphorus(V) 5,10,15,20-tetraalkylporphyrins for PDT

Ryan

Mothi

Petitdemange

et al. 2014

Photodiagnosis and Photodynamic Therapy

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SummaryImproved photosensitizers for use in photomedicine must possess good water-solubility and optimal photophysical properties. Phosphorus(V) porphyrins fulfill these criteria and are a class of porphyrins with significant potential applications in phototherapy. Five phosphorus(V) porphyrins bearing alkyl substituents have been synthesized. Reasonable to good yields were obtained for all P(V) insertions and all compounds underwent biological evaluation for their PDT activity on two esophageal cancer cell lines, OE33 and SKGT-4. Their cellular uptake was investigated using a high content screening method. Notably, three compounds displayed good uptake and using the MTS cell proliferation assay, two were shown to have photocytotoxicity comparable to mTHPC (Temoporfin®) with IC 50 values of 6.5 and 5.5 μM.2

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Synthesis, cellular internalization and photodynamic activity of glucoconjugated derivatives of tri and tetra(meta-hydroxyphenyl)chlorins

Cited by 119 publications

References 37 publications

Nucleophilic Aromatic Substitution on Pentafluorophenyl‐Substituted Dipyrranes and Tetrapyrroles as a Route to Multifunctionalized Chromophores for Potential Application in Photodynamic Therapy

Nucleophilic Aromatic Substitution on Pentafluorophenyl‐Substituted Dipyrranes and Tetrapyrroles as a Route to Multifunctionalized Chromophores for Potential Application in Photodynamic Therapy

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

Lead structures for applications in photodynamic therapy. 5. Synthesis and biological evaluation of water soluble phosphorus(V) 5,10,15,20-tetraalkylporphyrins for PDT

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