Tan-Sothea Ouk

Synthesis and photobiocidal properties of cationic porphyrin-grafted paper.

We report on the synthesis of cellulose paper bearing a cationic porphyrin, designed for antimicrobial applications. Tricationic porphyrin has been covalently grafted on paper, without previous chemical modification of the cellulosic support, using 1,3,5-triazine derivative as linker. The obtained porphyrin-grafted paper was characterized by infrared (ATR-FTIR), UV-visible and diffuse reflectance UV-vis (DRUV) spectroscopies to confirm the triazine linkage. Thermogravimetric analysis (TGA) was used to investigate thermal properties of grafted paper. Antimicrobial activity of porphyrin-cellulose material was tested under visible light irradiation against Staphylococcus aureus and Escherichia coli. The two bacterial strains deposited on the resulting photosensitizing filter paper are efficiently killed after illumination.

Hydrophilic chlorin-conjugated magnetic nanoparticles—Potential anticancer agent for the treatment of melanoma by PDT

This Letter reports the synthesis and the characterization of two new water-stable and soluble photosensitizer-conjugated magnetic nanoparticles (PS-MNPs) composed of an iron oxide magnetic core coated with a biocompatible dextran shell bearing polyaminated chlorin p6. Designed to improve cancer cell targeting, these photosensitizers were assayed for their antitumour activity against two variants of B16 mouse melanoma cell line (B16F10 and B16G4F, with or without melanin, respectively). Cell viability measurements demonstrated that PS-MNPs were more phototoxic than PEI-chlorin p6 making these photosensitizers promising for further in vitro and in vivo investigations.

LMP1-Induced Cell Death May Contribute to the Emergency of Its Oncogenic Property

Background and Objectives Epstein-Barr Virus (EBV) Latent Membrane Protein 1 (LMP1) is linked to a variety of malignancies including Hodgkins disease, lymphomas, nasopharyngeal and gastric carcinoma. LMP1 exerts its transforming or oncogenic activity mainly through the recruitment of intracellular adapters via LMP1 C-terminal Transformation Effector Sites (TES) 1 and 2. However, LMP1 is also reported to elicit significant cytotoxic effects in some other cell types. This cytotoxic effect is quite intriguing for an oncogenic protein, and it is unclear whether both functional aspects of the protein are related or mutually exclusive. Methodology and Principal Findings Using different ectopic expression systems in both Madin-Darby canine kidney (MDCK) epithelial cells and human embryonic kidney HEK-293 cells, we observe that LMP1 ectopic expression massively induces cell death. Furthermore, we show that LMP1-induced cytotoxicity mainly implies LMP1 C-terminal transformation effector sites and TRADD recruitment. However, stable expression of LMP1 in the same cells, is found to be associated with an increase of cell survival and an acquisition of epithelial mesenchymal transition phenotype as evidenced by morphological modifications, increased cell mobility, increased expression of MMP9 and decreased expression of E-cadherin. Our results demonstrate for the first time that the cytotoxic and oncogenic effects of LMP1 are not mutually exclusive but may operate sequentially. We suggest that in a total cell population, cells resistant to LMP1-induced cytotoxicity are those that could take advantage of LMP1 oncogenic activity by integrating LMP1 signaling into the pre-existent signaling network. Our findings thus reconcile the apparent opposite apoptotic and oncogenic effects described for LMP1 and might reflect what actually happens on LMP1-induced cell transformation after EBV infection in patients.

Synthesis and photobactericidal properties of a neutral porphyrin grafted onto lignocellulosic fibers.

Photodynamic antimicrobial chemotherapy (PACT), as one of the promising alternative antimicrobial treatment, has received great attention in recent years. In this work, a new antimicrobial material has been elaborated by grafting a neutral porphyrin, the metallated 5-(4-azidophenyl)-10,15,20-triphenylporphyrin, onto lignocellulosic fibers by using the Copper (I)-Catalyzed Alkyne-Azide 1,3-dipolar Cycloaddition (CuAAC) reaction. The cross-linked porphyrin-Kraft pulp material was characterized by infrared and by XPS spectroscopy analyses, which proved the covalent linkage between the porphyrin and propargylated Kraft pulp fibers. The antimicrobial activity of this material was tested under visible light irradiation with a low light dose (9.5 J/cm(2)) against Staphylococcus aureus and Pseudomonas aeruginosa. The two bacterial strains deposited on the resulting photosensitizing Kraft pulp are efficiently killed after illumination. Such materials could find applications in industrial, household and medical environments as an alternative to overcome the widespread microbial multiresistance to classical treatments.

Lysine Analogue of Polymyxin B as a Significant Opportunity for Photodynamic Antimicrobial Chemotherapy

In order to highlight the potential of photodynamic antimicrobial chemotherapy in case of infections by antibiotic resistant-strains, a new antimicrobial peptide conjugate has been synthesized, consisting of a derivative of polymyxin B and a cationic porphyrin covalently attached together to a spacer. A polymyxin-derived moiety was subjected to a primary structural modification in the replacement of four diaminobutyrate residues with lysine ones. This modification was done in order to strongly reduce bactericidal activity, with the aim to eliminate the potential rise of polymyxin-resistant strains. Despite this modification, this new conjugate displayed a strong photobactericidal activity against Gram-positive as well as Gram-negative bacteria. It was further shown that this conjugate was able to strongly stick to the cell walls of either kind of strain, thus helping to inactivate bacteria through the production of reactive oxygen species under light irradiation.

Novel polycarboxylate porphyrins: Synthesis, characterization, photophysical properties and preliminary antimicrobial study against Gram-positive bacteria

We describe the synthesis, characterization and photophysical properties of two new polycarboxylic photosensitizers. Owing to their structural design, these two compounds show water solubilities larger than natural carboxylic photosensitizers (e.g., protoporphyrin IX, hematoporphyrin, etc.) and also good singlet oxygen quantum yields. These compounds were tested as photo-antimicrobial agents against Staphylococcus aureus and Bacillus cereus strains. Results reveal that their photocytotoxicities are strongly dependent on their amphiphilic character and more precisely the number and position of the carboxylic acid and mesityl substituents.

Enhancement of photobactericidal activity of chlorin-e6-cellulose nanocrystals by covalent attachment of polymyxin B

Despite the advances made over the last decade, infections caused by multi-drug resistant bacterial strains are increasingly important societal issues that need to be addressed. New approaches have already been developed in order to overcome this problem. Photodynamic antimicrobial chemotherapy (PACT) could provide an alternative to fight infectious bacteria. This approach has already inspired the development of innovative materials. Interesting results have been obtained against Gram-positive bacteria, but it also appeared that Gram-negative strains, especially Pseudomonas aeruginosa, were less sensitive to PACT. Enhanced efficacy against Gram-negative bacteria had been previously obtained with photosensitizers bound to antimicrobial peptides. In this work, we designed a photobactericidal organic material, CNCsc6-PMB, consisting of cellulose nanocrystals to which the photosensitizer chlorin-e6 and the antimicrobial polypeptide polymyxin B (PMB) were covalently attached. These modified nanocrystals were characterized by IR spectroscopy, zeta potential measurements and elemental analyses, after which antibacterial assays were carried out. Following light irradiation, CNCsc6-PMB demonstrated efficiency against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis) by inhibition of bacterial growth. An amplifying effect of chlorin-e6 has been highlighted against these Gram-negative strains, based on membrane weakening and a potential docking effect from the polymyxin moiety. Such results confirmed the importance of using an antimicrobial peptide in order to broaden the spectrum of PACT.

Synthesis And Biological Evaluation Of Nitrogen Mustard Derivatives Of Purine Bases

This paper deals with the synthesis of nitrogen mustard analogs, derivatives of purine bases. Alkylation in position N-9 and diethanolamine fixation on position 6 were managed by microwave irradiations. Chlorination of these dihydroxylated intermediates led to a cyclization, giving tricyclic purine base analogs bearing a chloroethyl chain. Finally, MTT assays on obtained compounds do not show cytotoxicity on four different cancer cell lines.

Synthesis and antibacterial properties of thymol and carvacrol grafted onto lignocellulosic kraft fibers

Bacterial infections and surface contaminations are worrying public health issues. It becomes urgent to find solutions. One of the ways to limit bacterial proliferation is to develop new antimicrobial materials. The phenolic compounds of essential oils like thymol and carvacrol, are attractive antibacterial candidates, which have gained great popularity in the food, cosmetic, and pharmaceutical industries. This work describes the elaboration of bioinspired antibacterial materials. Thymol and carvacrol are linked to kraft pulp fibers, via triazine link. This novel material has been investigated for its antibacterial properties against Escherichia coli and Staphylococcus aureus. The developed materials show very interesting antibacterial activity. The grafting of thymol and carvacrol by covalent bond allows to avoid the problem of their release and, thus, could maintain the antibacterial properties of support.

Synthesis and Biological Evaluations of Click-Generated Nitrogen Mustards

This paper describes the synthesis of new click-generated nitrogen mustards and their biological evaluation. By using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, we managed to synthesize eight new nitrogen mustards. This strategy paves the way for the synthesis of a new family of nitrogen mustard, with an important structural variability. Furthermore, we studied the biological activity of synthesized compounds by testing their cytotoxicity on four representative cancer cell lines A431, JURKAT, K562, and U266. One structure, 1-benzyl-4-(N,N-di-2-chloroethylaminomethyl)-1H-[1,2,3]triazole, showed an interesting cytotoxic effect.