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Umbelliferone Decorated Water-soluble Zinc(II) Phthalocyanines - In Vitro Phototoxic Antimicrobial Anti-cancer Agents.

ABSTRACT: In this contribution we report on the synthesis, characterization and application of water-soluble zinc(II) phthalocyanines, which are decorated with four or eight umbelliferone moieties for photodynamic therapy (PDT). These compounds are linked peripherally to zinc(II) phthalocyanine by a triethylene glycol linker attached to pyridines, leading to cationic pyridinium units, able to increase the water solubility of the system. Beside their photophysical properties they were analyzed concerning their cellular distribution in human hepatocyte carcinoma (HepG2) cells as well as their phototoxicity towards HepG2 cells, Gram-positive (S. aureus strain 3150/12 and B. subtilis strain DB104) and Gram-negative bacteria (E. coli strain UTI89 and E. coli strain Nissle 1917). At low light doses and concentrations, they exhibit superb antimicrobial activity against Gram-positive bacteria as well as anti-tumor activity against HepG2. They are even capable to inactivate Gram-negative bacteria, whereas the dark toxicity remains low. These unique water-soluble compounds can be regarded as all-in-one type photosensitizers with broad applications ranges in the future.

SUBMITTER: Sowa A

PROVIDER: S-EPMC8596868 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Synthesis and Anticancer Properties of Water-Soluble Zinc Ionophores 2

Project description:We have demonstrated that water-soluble zinc ionophores can be administered to mice at relatively high doses and inhibit the growth of A549 lung cancer cells grown in xenograft models. Gene expression profiles of tumor specimens harvested from mice four hours after treatment confirmed that the activation of stress responsive genes occurs in vivo. These findings lead us to propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Keywords: Dose response

2007-02-07 | GSE6962 | GEO

Synthesis and Anticancer Properties of Water-Soluble Zinc Ionophores 1

Project description:We have shown that water solubilized versions of a zinc ionophore increase intracellular concentrations of free zinc and have antiproliferative activity in exponential phase A549 lung cancer cultures. The gene expression profiles of A549 lung cancer cultures treated with the lead compound PCI-5002 reveal the activation of stress response pathways. Medium supplementation with zinc (25 μM) led to activation of additional oxidative stress response as well as apoptotic pathways. We propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Keywords: Dose response

2007-02-07 | GSE6960 | GEO

Water-soluble benzylidene cyclopentanone based photosensitizers for in vitro and in vivo antimicrobial photodynamic therapy.

Project description:Antimicrobial photodynamic therapy (aPDT) has been proposed to cope with the increasing antibiotic resistance among pathogens. As versatile pharmacophores, benzylidene cyclopentanone based photosensitizers (PSs) have been used in various bioactive materials. However, their reports as aPDT agents are very limited, and relationships between their chemical structures and antibacterial abilities have not been systematically discussed. Here, nine water-soluble benzylidene cyclopentanone PSs modified by polyethylene glycol (PEG), carboxylate anionic or pyridyl cationic agents are studied for aPDT. It is found that the binding/uptake abilities and aPDT effects of these PSs toward bacterial cells vary significantly when adjusting the number and position of their terminal charged groups. Though the comparable (also best) binding/uptake amounts are achieved by both cationic PS P3 and anionic PS Y1, only Y1 exhibits much more excellent aPDT activities than other PSs. Antibacterial mechanisms reveal that, relative to the favorable cell wall-binding of cationic PS P3, the anionic PS Y1 can accumulate more in the spheroplast/protoplast of methicillin-resistant Staphylococcus aureus (MRSA), which ensures its high efficient aPDT abilities both in vitro and in vivo. This study suggests the great clinical application potential of Y1 in inactivation of MRSA.

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A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative.

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Preparation and In Vitro Photodynamic Activity of Glucosylated Zinc(II) Phthalocyanines as Underlying Targeting Photosensitizers.

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Tetracycline Water Soluble Formulations with Enhanced Antimicrobial Activity.

Project description:The negligible water solubility of tetracycline (TC), a well-known antibiotic of clinical use, is the major disadvantage for its oral administration. With the aim to improve the water solubility of TC, the micelles of formulae SLS@TC and CTAB@TC (SLS = sodium lauryl sulphate and CTAB = cetrimonium bromide) were synthesized. The micelles SLS@TC and CTAB@TC were characterized by melting point (m.p.), thermogravimetric differential thermal analysis (TG-DTA), differential scanning calorimetry (DTG/DSC), attenuated total reflection spectroscopy (FT-IR-ATR), ultra-violet visible (UV/vis) spectroscopy, proton nucleus magnetic resonance (1H-NMR) spectroscopy, and the ultrasonically-induced biregringence technique. The antimicrobial activity of SLS@TC and CTAB@TC was evaluated, by means of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and inhibition zone (IZ), against the Gram negative bacterial strains Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli) and the Gram positive ones of the genus of Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus). Generally, both micelles show better activity than that of TC against the microbial strains tested. Thus, the MIC value of CTAB@TC is 550-fold higher than that of free TC against S. epidermidis. Despite the stronger activity of CTAB@TC than SLS@TC against both Gram negative and Gram positive microbes, SLS@TC is classified as a bactericidal agent (in that it eliminates 99.9% of the microbes), in contrast to CTAB@TC, which is bacteriostatic one (inhibits, but does not kill the organisms). The toxicity of SLS@TC and CTAB@TC was evaluated against human corneal eukaryotic cells (HCECs). Moreover, SLS@TC and CTAB@TC exhibit low in vivo toxicity against Artemia salina, even at concentrations up to threefold higher than those of their MICmax. Therefore, SLS@TC and CTAB@TC can be candidates for the development of new antibiotics.

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Synthesis and anticancer properties of water-soluble zinc ionophores.

Project description:Several water-solubilized versions of the zinc ionophore 1-hydroxypyridine-2-thione (ZnHPT), synthesized as part of the present study, have been found both to increase the intracellular concentrations of free zinc and to produce an antiproliferative activity in exponential phase A549 human lung cancer cultures. Gene expression profiles of A549 cultures treated with one of these water-soluble zinc ionophores, PCI-5002, reveal the activation of stress response pathways under the control of metal-responsive transcription factor 1 (MTF-1), hypoxia-inducible transcription factor 1 (HIF-1), and heat shock transcription factors. Additional oxidative stress response and apoptotic pathways were activated in cultures grown in zinc-supplemented media. We also show that these water-soluble zinc ionophores can be given to mice at 100 micromol/kg (300 micromol/m(2)) with no observable toxicity and inhibit the growth of A549 lung and PC3 prostate cancer cells grown in xenograft models. Gene expression profiles of tumor specimens harvested from mice 4 h after treatment confirmed the in vivo activation of MTF-1-responsive genes. Overall, we propose that water-solubilized zinc ionophores represent a potential new class of anticancer agents.

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Water-Soluble Phthalocyanines Selectively Bind to Albumin Dimers: A Green Approach Toward Enhancing Tumor-Targeted Photodynamic Therapy.

Project description:Targeted delivery of therapeutic agents is of particular interest in the field of cancer treatment. However, there is an urgent need for developing clinically promising targeting approaches that can be readily administered in a green manner. Methods: Five phthalocyanine derivatives bearing different anionic and cationic groups were designed and synthesized. Then, their binding affinity with albumin were studied using gel assays, optical spectra and computational simulation. Finally, in vitro and in vivo fluorescence imaging and photodynamic therapy (PDT) evaluations were carried out. Results: The two positively charged compounds could selectively bind to albumin dimer over albumin monomer, while the three negatively charged phthalocyanines could bind to both albumin monomer and dimer. Following systemic administration, the phthalocyanines show improved tumor accumulation via transport by natural albumin. PDT evaluations indicate that one of the positively charged compounds, ZnPcN4, shows outstanding phototherapeutic efficacy against tumors in preclinical models. Conclusion: Our findings demonstrate that the use of water-soluble phthalocyanines as photosensitizers and in vivo albumin as a natural carrier may provide a green and efficient approach for tumor-targeted imaging and therapy.

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The use of water-soluble phthalocyanines as textile dyes in nylon/elastane fabric: fastness and antibacterial effectiveness.

Project description:This work reports on dyeing of nylon/elastane fabric with water-soluble phthalocyanines ( 1-4 ) bearing quinoline 5-sulfonic acid substituents on the peripheral or nonperipheral positions and determining the antibacterial efficiency of the phthalocyanine compounds and the dyed nylon/elastane fabrics. The light, washing, water, perspiration, and rubbing fastness properties of nylon/elastane fabrics dyed with phthalocyanines were also determined. The results showed that all dyed fabrics showed very good wet fastness values. The lightfastness value of the nylon/elastane fabric dyed with phthalocyanine dye ( 1 ) showed a much better value than the others. Also, the antibacterial efficiencies of the dyed nylon fabrics and the dye compounds were investigated against a gram-negative ( Escherichia coli ) and a grampositive ( Staphylococcus aureus ) bacteria by using disc diffusion method. The results showed that the dyed nylon/elastane fabrics and the compounds exhibited antibacterial activities against both bacteria.

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Synthesis and Anticancer Properties of Water-Soluble Zinc Ionophore: Cell Culture and Xenograft Model

Project description:This SuperSeries is composed of the SubSeries listed below.

2007-02-07 | GSE6972 | GEO