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1.
Photochem Photobiol Sci ; 23(3): 395-407, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38300464

RESUMO

Despite advances achieved in the health field over the last decade, infections caused by resistant bacterial strains are an increasingly important societal issue that needs to be addressed. New approaches have already been developed to overcome this problem. Photodynamic antimicrobial chemotherapy (PACT) could provide a promising alternative method to eradicate microbes. This approach has already inspired the development of innovative surfaces. Interesting results were achieved against Gram-positive bacteria, but it also appeared that Gram-negative strains, especially Pseudomonas aeruginosa, were less sensitive to PACT. However, materials coated with cationic porphyrins have already proven their wide-spectrum activity, but these materials were not suitable for industrial-scale production. The main aim of this work was the design of a large-scale evolutionary material based on PACT and antibiotic prophylaxis. Transparent regenerated cellulose has been simply impregnated with a usual cationic porphyrin (N-methylpyridyl) and an antimicrobial peptide (polymyxin B). In addition to its photophysical properties, this film exhibited a wide-spectrum bactericidal activity over 4 days despite daily application of fresh bacterial inoculums. The efficiency of PACT and polymyxin B combination could help to reduce the emergence of bacterial multi-resistant strains and we believe that this kind of material would provide an excellent opportunity to prevent bacterial contamination of bandages or packaging.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Polimixina B/farmacologia , Fotoquimioterapia/métodos , Bactérias , Bactérias Gram-Positivas , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana
2.
Chem Biodivers ; 21(2): e202300494, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37983920

RESUMO

This study provides a comprehensive overview of the current knowledge regarding phototoxic terrestrial plants and their phototoxic and photosensitizing metabolites. Within the 435,000 land plant species, only around 250 vascular plants have been documented as phototoxic or implicated in phototoxic occurrences in humans and animals. This work compiles a comprehensive catalog of these phototoxic plant species, organized alphabetically based on their taxonomic family. The dataset encompasses meticulous details including taxonomy, geographical distribution, vernacular names, and information on the nature and structure of their phototoxic and photosensitizing molecule(s). Subsequently, this study undertook an in-depth investigation into phototoxic molecules, resulting in the compilation of a comprehensive and up-to-date list of phytochemicals exhibiting phototoxic or photosensitizing activity synthesized by terrestrial plants. For each identified molecule, an extensive review was conducted, encompassing discussions on its phototoxic activity, chemical family, occurrence in plant families or species, distribution within different plant tissues and organs, as well as the biogeographical locations of the producer species worldwide. The analysis also includes a thorough discussion on the potential use of these molecules for the development of new photosensitizers that could be used in topical or injectable formulations for antimicrobial and anticancer phototherapy as well as manufacturing of photoactive devices.


Assuntos
Dermatite Fototóxica , Fármacos Fotossensibilizantes , Humanos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Plantas
3.
Photochem Photobiol Sci ; 21(1): 113-145, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34784052

RESUMO

Antimicrobial resistance is threatening to overshadow last century's medical advances. Etiological agents of previously eradicated infectious diseases are now resurgent as multidrug-resistant strains, especially for Gram-negative strains. Finding new therapeutic solutions is a real challenge for our society. In this framework, Photodynamic Antimicrobial ChemoTherapy relies on the generation of toxic reactive oxygen species in the presence of light, oxygen, and a photosensitizer molecule. The use of reactive oxygen species is common for disinfection processes, using chemical agents, such as chlorine and hydrogen peroxide, and as they do not have a specific molecular target, it decreases the potential of tolerance to the antimicrobial treatment. However, light-driven generated reactive species result in an interesting alternative, as reactive species generation can be easily tuned with light irradiation and several PSs are known for their low environmental impact. Over the past few years, this topic has been thoroughly studied, exploring strategies based on single-molecule PSs (tetrapyrrolic compounds, dipyrrinate derivatives, metal complexes, etc.) or on conjunction with delivery systems. The present work describes some of the most relevant advances of the last 6 years, focusing on photosensitizers design, formulation, and potentiation, aiming for the disinfection of Gram-negative bacteria.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Antibacterianos , Desinfecção , Bactérias Gram-Negativas , Fármacos Fotossensibilizantes/farmacologia
4.
Molecules ; 26(4)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672630

RESUMO

Despite advances achieved over the last decade, infections caused by multi-drug-resistant bacterial strains are increasingly becoming 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. Many studies have highlighted the value of cationic photosensitizers in order to improve this approach. This study reports the synthesis and the characterization of cationic porphyrins derived from methylimidazolium and phenylimidazolium porphyrins, along with a comparison of their photophysical properties with the well-known N-methylpyridyl (pyridinium) porphyrin family. PACT tests conducted with the tetracationic porphyrins of these three families showed that these new photosensitizers may offer a good alternative to the classical pyridinium porphyrins, especially against S.aureus and E.coli. In addition, they pave the way to new cationic photosensitizers by the means of derivatization through amide bond formation.


Assuntos
Antibacterianos/farmacologia , Imidazóis/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Piridinas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Imidazóis/síntese química , Imidazóis/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/síntese química , Porfirinas/química , Pseudomonas aeruginosa/efeitos dos fármacos , Piridinas/síntese química , Piridinas/química , Staphylococcus aureus/efeitos dos fármacos
5.
Photochem Photobiol Sci ; 19(4): 445-461, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32104827

RESUMO

Antimicrobial resistance is threatening to overshadow last century's medical advances. Previously eradicated infectious diseases are now resurgent as multi-drug resistant strains, leading to expensive, toxic and, in some cases, ineffective antimicrobial treatments. Given this outlook, researchers are willing to investigate novel antimicrobial treatments that may be able to deal with antimicrobial resistance, namely photodynamic therapy (PDT). PDT relies on the generation of toxic reactive oxygen species (ROS) in the presence of light and a photosensitizer (PS) molecule. PDT has been known for almost a century, but most of its applications have been directed towards the treatment of cancer and topical diseases. Unlike classical antimicrobial chemotherapy treatments, photodynamic antimicrobial chemotherapy (PACT) has a non-target specific mechanism of action, based on the generation of ROS, working against cellular membranes, walls, proteins, lipids and nucleic acids. This non-specific mechanism diminishes the chances of bacteria developing resistance. However, PSs usually are large molecules, prone to aggregation, diminishing their efficiency. This review will report the development of materials obtained from natural sources, as delivery systems for photosensitizing molecules against microorganisms. The present work emphasizes on the biological results rather than on the synthesis routes to prepare the conjugates. Also, it discusses the current state of the art, providing our perspective on the field.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Materiais Biocompatíveis/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antibacterianos/química , Materiais Biocompatíveis/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo
6.
Photochem Photobiol Sci ; 17(11): 1780-1786, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30167617

RESUMO

We report the preparation of a cellulose fabric bearing derivative protoporphyrin IX units covalently attached to the cellulose backbone of a fabric. Ce(IV) redox system radical polymerization was used to polymerize methacrylic acid (MAA) onto a cotton material and to obtain cotton-g-polyMAA. Attachment of the photosensitizer, a protoporphyrin IX (PpIX) amino derivative, on cotton-g-polyMAA was realized successfully by a classical peptidic covalent link. The modified surfaces were characterized by ATR-FTIR, DRUV, TGA, and SEM methods. Under visible light irradiation, protoporphyrinic cotton showed antibacterial activity against Staphyloccoccus aureus. This concept is very promising in the field of bacterial decontamination (sterile area, hospital equipment, etc.).


Assuntos
Antibacterianos/farmacologia , Celulose/farmacologia , Escherichia coli/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Celulose/síntese química , Celulose/química , Cério/química , Cério/farmacologia , Luz , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Protoporfirinas/química , Protoporfirinas/farmacologia , Têxteis
7.
Bioconjug Chem ; 28(9): 2493-2506, 2017 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-28853858

RESUMO

A novel compound consisting of a cationic porphyrin covalently attached to a derivative of polymyxin B has been synthesized and presents enhanced activity and targeting properties compared to the usual cationic porphyrins recognized as efficient photosensitizers in photodynamic antimicrobial chemotherapy (PACT). A synthesis pathway was established to preserve the bactericidal activity of the peptide. Accordingly, the N-terminal amino acid (l-2,4-diaminobutyric acid) of polymyxin B (PMB) was switched for a cysteine residue. Then, the resulting derivative of PMB was covalently bound to 5-(4-aminophenyl)-10,15,20-tri(4-N-methylpyridyl)-21H,23H-porphyrin using a thiol-maleimide "click" coupling. The peptide-coupled photosensitizer has demonstrated an improved PACT efficiency compared to the cationic porphyrin alone. This enhancement has been observed against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli in particular. Flow cytometry analyses and confocal imaging microscopy demonstrated that the porphyrin-peptide conjugate selectively adhered to the cell walls of either Gram-positive or Gram-negative bacteria, thus justifying the damages induced by singlet oxygen production.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Polimixina B/farmacologia , Porfirinas/farmacologia , Antibacterianos/química , Infecções Bacterianas/tratamento farmacológico , Cátions/química , Cátions/farmacologia , Linhagem Celular , Escherichia coli/efeitos dos fármacos , Humanos , Fármacos Fotossensibilizantes/química , Polimixina B/química , Porfirinas/química , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
8.
Bioorg Med Chem Lett ; 25(2): 355-62, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25475206

RESUMO

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.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Ácidos Carboxílicos/química , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Bactérias Gram-Positivas/crescimento & desenvolvimento , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Luz , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Fotoquímica , Fármacos Fotossensibilizantes/síntese química , Porfirinas/síntese química , Oxigênio Singlete/química , Relação Estrutura-Atividade
9.
Antonie Van Leeuwenhoek ; 106(4): 693-706, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25090957

RESUMO

Probiotics represent a potential strategy to influence the host's immune system thereby modulating immune response. Lipoteichoic Acid (LTA) is a major immune-stimulating component of Gram-positive cell envelopes. This amphiphilic polymer, anchored in the cytoplasmic membrane by means of its glycolipid component, typically consists of a poly (glycerol-phosphate) chain with D-alanine and/or glycosyl substitutions. LTA is known to stimulate macrophages in vitro, leading to secretion of inflammatory mediators such as Nitric Oxide (NO). This study investigates the structure-activity relationship of purified LTA from three probiotic Bacillus strains (Bacillus cereus CH, Bacillus subtilis CU1 and Bacillus clausii O/C). LTAs were extracted from bacterial cultures and purified. Chemical modification by means of hydrolysis at pH 8.5 was performed to remove D-alanine. The molecular structure of native and modified LTAs was determined by (1)H NMR and GC-MS, and their inflammatory potential investigated by measuring NO production by RAW 264.7 macrophages. Structural analysis revealed several differences between the newly characterized LTAs, mainly relating to their D-alanylation rates and poly (glycerol-phosphate) chain length. We observed induction of NO production by LTAs from B. subtilis and B. clausii, whereas weaker NO production was observed with B. cereus. LTA dealanylation abrogated NO production independently of the glycolipid component, suggesting that immunomodulatory potential depends on D-alanine substitutions. D-alanine may control the spatial configuration of LTAs and their recognition by cell receptors. Knowledge of molecular mechanisms behind the immunomodulatory abilities of probiotics is essential to optimize their use.


Assuntos
Alanina/análise , Alanina/imunologia , Bacillus/química , Lipopolissacarídeos/análise , Lipopolissacarídeos/imunologia , Probióticos/química , Ácidos Teicoicos/análise , Ácidos Teicoicos/imunologia , Animais , Bacillus/imunologia , Linhagem Celular , Cromatografia Gasosa-Espectrometria de Massas , Hidrólise , Fatores Imunológicos/análise , Fatores Imunológicos/química , Fatores Imunológicos/imunologia , Lipopolissacarídeos/química , Macrófagos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Relação Estrutura-Atividade , Ácidos Teicoicos/química
10.
J Virol ; 86(7): 3934-43, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22258264

RESUMO

Epstein-Barr virus (EBV) is a common human herpesvirus. Infection with EBV is associated with several human malignancies in which the virus expresses a set of latent proteins, among which is latent membrane protein 1 (LMP1). LMP1 is able to transform numerous cell types and is considered the main oncogenic protein of EBV. The mechanism of action is based on mimicry of activated members of the tumor necrosis factor (TNF) receptor superfamily, through the ability of LMP1 to bind similar adapters and to activate signaling pathways. We previously generated two unique models: a monocytic cell line and a lymphocytic (NC5) cell line immortalized by EBV that expresses the type II latency program. Here we generated LMP1 dominant negative forms (DNs), based on fusion between green fluorescent protein (GFP) and transformation effector site 1 (TES1) or TES2 of LMP1. Then we generated cell lines conditionally expressing these DNs. These DNs inhibit NF-κB and Akt pathways, resulting in the impairment of survival processes and increased apoptosis in these cell lines. This proapoptotic effect is due to reduced interaction of LMP1 with specific adapters and the recruitment of these adapters to DNs, which enable the generation of an apoptotic complex involving TRADD, FADD, and caspase 8. Similar results were obtained with cell lines displaying a latency III program in which LMP1-DNs decrease cell viability. Finally, we prove that synthetic peptides display similar inhibitory effects in EBV-infected cells. DNs derived from LMP1 could be used to develop therapeutic approaches for malignant diseases associated with EBV.


Assuntos
Transformação Celular Viral , Regulação para Baixo , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/fisiologia , Linfócitos T/virologia , Proteínas da Matriz Viral/metabolismo , Apoptose , Linhagem Celular , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/fisiopatologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/crescimento & desenvolvimento , Humanos , Transdução de Sinais , Linfócitos T/citologia , Linfócitos T/metabolismo , Proteínas da Matriz Viral/genética , Latência Viral
11.
Bioorg Med Chem Lett ; 23(9): 2486-90, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23541648

RESUMO

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.


Assuntos
Antineoplásicos/química , Nanopartículas de Magnetita/química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Animais , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Luz , Nanopartículas de Magnetita/ultraestrutura , Melanoma Experimental/tratamento farmacológico , Camundongos , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/toxicidade , Temperatura
12.
Gels ; 9(2)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36826294

RESUMO

In the present work, we report on the synthesis of light-triggered antibacterial hydrogels, based on xylan chains covalently bound to meso-tetra(4-carboxyphenyl)porphyrin (TCPP). Not only does TCPP act as a photosensitizer efficient against Gram-positive bacteria, but it also serves as a cross-linking gelator, enabling the simple and easy building of xylan conjugate hydrogels. The hydrogels were characterized by infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), along with swelling and rheological tests. The antimicrobial activity of the hydrogels was tested under visible light irradiation against two Gram-positive bacterial strains, Staphylococcus aureus and Bacillus cereus. The preliminary results showed an interesting activity on these bacteria, indicating that these hydrogels could be of great potential in the treatment of skin bacterial infections with this species by photodynamic antimicrobial chemotherapy (PACT).

13.
J Biomol Struct Dyn ; 41(10): 4711-4722, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35532093

RESUMO

A novel potentially biologically active oxazaphosphinane derivatives was synthesized by facile synthetic approaches from the combination of hydroxyaniline, aldehyde, and triethylphosphite. The crystal structure of compound 1b has been determined. Single crystals belong to the triclinic system with p - 1 space. The relative in vitro antitumor activity against human cell lines (PRI, K562, and JURKAT) of these derivatives in comparison to chlorombucil is reported. All synthesized compound showed excellent activity with IC50 value of 0.014-0.035 mM. The binding energy of the Epidermal growth factor receptor (EGFR)-oxazaphosphinane complex and the calculated inhibition constant using docking simulation showed that all molecules has the ability to inhibit EGFR therapeutic target. In addition, DFT calculation has been used to analyze the electronic and geometric characteristics.Communicated by Ramaswamy H. Sarma.


Assuntos
Antineoplásicos , Humanos , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Proliferação de Células , Antineoplásicos/química , Cristalografia por Raios X , Receptores ErbB/metabolismo , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais
14.
RSC Adv ; 13(28): 19567-19584, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37388149

RESUMO

The objective of this study is to evaluate a series of molecules based on cyclosulfamide as potential anticancer agents. Additionally, the study aims to analyze the obtained results through in silico studies; by conducting experiments and utilizing theoretical methods. In this context, we investigated the cytotoxic activity of enastron analogues on three human cell lines PRI (lymphoblastic cell line) derived from B-cell lymphoma. JURKAT (ATCC TIB-152) acute T cell leukaemia and K562 (ATCC CLL-243) is a chronic myelogenous leukaemia. Most of the tested compounds showed good inhibitory activity compared with the reference ligand (chlorambucil). The 5a derivative demonstrated the strongest effect against all cancer cells used. Furthermore, molecular docking simulations of the Eg5-enastron analogue complex revealed that studied molecules have the ability to inhibit the Eg5 enzyme, as evidenced by their calculated docking score. Following the promising results from the molecular docking study, the complex Eg5-4a underwent a 100 ns molecular dynamics simulation using Desmond. During the simulation, the receptor-ligand pairing demonstrated substantial stability after the initial 70 ns. In addition, we used DFT calculations to analyze the electronic and geometric characteristics of the studied compounds. The HOMO and LUMO band gap energies, and the molecular electrostatic potential surface were also deducted for the stable structure of each compound. Also, we studied the prediction of absorption, distribution, metabolism and excretion (ADME) of the compounds.

15.
Antioxidants (Basel) ; 12(10)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37891873

RESUMO

An ultrasound-enzyme-assisted extraction (UEAE) was optimized to extract, simultaneously, the hydrophilic and lipophilic compounds from three berry pomaces (raspberry, strawberry and blackberry). First, an enzyme screening designated a thermostable alkaline protease as the most suitable enzyme to recover, in an aqueous medium, the highest yields of polyphenols and oil in the most efficient way. Secondly, the selected enzyme was coupled to ultrasounds (US) in sequential and simultaneous combinations. The simultaneous US-alkaline enzyme combination was selected as a one-single-step process and was then optimized by definitive screening design (DSD). The optimized parameters were: US amplitude, 20% (raspberry pomace) or 70% (strawberry and blackberry pomaces); pH, 8; E/S ratio, 1% (w/w); S/L ratio, 6% (w/v); extraction time, 30 min; temperature, 60 °C. Compared to conventional extractions using organic solvents, the UEAE extracted all the polyphenols, with around 75% of the active polyphenols (measured by the DPPH● method) and up to 75% of the initial oil from the berry pomaces. Characterized lipophilic compounds were rich in polyunsaturated fatty acids (PUFAs), tocols and phytosterols. The polyphenolics were analyzed by UPLC-MS/MS; characteristic ellagitannins of the Rosaceae family (sanguiin H-6 or agrimoniin, sanguiin H-10, …) and ellagic acid conjugates were found as the major components.

16.
ACS Infect Dis ; 8(8): 1509-1520, 2022 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-35892255

RESUMO

The increase of antimicrobial resistance to conventional antibiotics is worldwide a major health problem that requires the development of new bactericidal strategies. Antimicrobial photodynamic therapy (a-PDT) that generates reactive oxygen species acting on multiple cellular targets is unlikely to induce bacterial resistance. This localized treatment requires, for safe and efficient treatment of nonsuperficial infections, a targeting photosensitizer excited in the near IR. To this end, a new conjugate consisting of an antimicrobial peptide linked to a π-extended porphyrin photosensitizer was designed for a-PDT. Upon irradiation at 720 nm, the conjugate has shown at micromolar concentration strong bactericidal action on both Gram-positive and Gram-negative bacteria. Moreover, this conjugate allows one to reach a low minimum bactericidal concentration with near IR excitation without inducing toxicity to skin cells.


Assuntos
Fotoquimioterapia , Porfirinas , Antibacterianos/farmacologia , Peptídeos Antimicrobianos , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia
17.
ACS Appl Bio Mater ; 4(9): 7204-7212, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-35006952

RESUMO

Photodynamic antimicrobial chemotherapy or PACT has been shown to be a promising antibacterial treatment that could overcome the challenge of multidrug-resistant bacteria. However, the use of most existing photosensitizers has been severely hampered by their significant self-quenching effect, poor water solubility, lack of selectivity against bacterial cells, and possible damage to the surrounding tissues. The use of hydrogels may overcome some of these limitations. We herein report a simple strategy to synthesize a cross-linked hydrogel from beech xylan. The hydrogel showed a high swelling ratio, up to 62, an interconnected porous structure, and good mechanical integrity, and 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetraiodide (TMPyP) was chosen as a model of hydrophilic photosensitizer (PS) and was encapsulated inside the xylan-based hydrogel. TMPyP-loaded hydrogel prolonged release of PS up to 24 h with a cumulative amount that could reach 100%. TMPyP-loaded hydrogel showed a photocytotoxic effect against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus strains, and Bacillus cereus, while no cytotoxicity was observed in the dark.


Assuntos
Anti-Infecciosos , Hidrogéis , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Escherichia coli , Hidrogéis/química , Fármacos Fotossensibilizantes/farmacologia , Xilanos/farmacologia
18.
Antibiotics (Basel) ; 10(6)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34074067

RESUMO

The increasing number of hospital-acquired infections demand the development of innovative antimicrobial treatments. Antimicrobial photodynamic therapy (aPDT) is a versatile technique which relies on the production of reactive oxygen species (ROS) generated by light-irradiated photosensitizers (PS) in the presence of oxygen (O2). 1H-Phenalen-1-one is a very efficient photosensitizer known for its high singlet oxygen quantum yield and its antimicrobial potential in aPDT when covalently bound to quaternary ammonium groups. Triazolium salts are stable aromatic quaternary ammonium salts that recently appeared as interesting moieties endowed with antimicrobial activities. The coupling between phenalenone and triazolium groups bearing various substituents was realized by copper-catalyzed azide-alkyne cycloaddition followed by alkylation with methyl iodide or 2-(bromomethyl)-1H-phenalen-1-one. As expected, most of the compounds retained the initial singlet oxygen quantum yield, close to unity. Minimum inhibitory concentrations (MIC) of 14 new phenalenone-triazolium salt derivatives and 2 phenalenone-triazole derivatives were determined against 6 bacterial strains (Gram-negatives and Gram-positives species). Most of these PS showed significant photoinactivation activities, the strongest effects being observed against Gram-positive strains with as low as submicromolar MIC values.

19.
Antibiotics (Basel) ; 10(5)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946390

RESUMO

Lignin has recently attracted the attention of the scientific community, as a suitable raw material for biomedical applications. In this work, acetylated lignin was used to encapsulate five different porphyrins, aiming to preserve their photophysical properties, and for further use as antibacterial treatment. The obtained nanoparticles were physically characterized, through dynamic light scattering size measurement, polydispersity index and zeta potential values. Additionally, the photophysical properties of the nanoparticles, namely UV-vis absorption, fluorescence emission, singlet oxygen production and photobleaching, were compared with those of the free porphyrins. It was found that all the porphyrins were susceptible to encapsulation, with an observed decrease in their fluorescence quantum yield and singlet oxygen production. These nanoparticles were able to exert an effective photodynamic bactericide effect (blue-LED light, 450-460 nm, 15 J/cm2) on Staphylococcus aureus and Escherichia coli. Furthermore, it was achieved a photodynamic bactericidal activity on an encapsulated lipophillic porphyrin, where the free porphyrin failed to diminish the bacterial survival. In this work it was demonstrated that acetylated lignin encapsulation works as a universal, cheap and green material for the delivery of porphyrins, while preserving their photophysical properties.

20.
Pharmaceutics ; 12(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066200

RESUMO

Antimicrobial photodynamic therapy (aPDT) also known as photodynamic inactivation (PDI) is a promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria. This therapy relies on the use of a molecule called photosensitizer capable of generating, from molecular oxygen, reactive oxygen species including singlet oxygen under light irradiation to induce bacteria inactivation. Ru(II) polypyridyl complexes can be considered as potential photosensitizers for aPDT/PDI. However, to allow efficient treatment, they must be able to penetrate bacteria. This can be promoted by using nanoparticles. In this work, ruthenium-polylactide (RuPLA) nanoconjugates with different tacticities and molecular weights were prepared from a Ru(II) polypyridyl complex, RuOH. Narrowly-dispersed nanoparticles with high ruthenium loadings (up to 53%) and an intensity-average diameter < 300 nm were obtained by nanoprecipitation, as characterized by dynamic light scattering (DLS). Their phototoxicity effect was evaluated on four bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa) and compared to the parent compound RuOH. RuOH and the nanoparticles were found to be non-active towards Gram-negative bacterial strains. However, depending on the tacticity and molecular weight of the RuPLA nanoconjugates, differences in photobactericidal activity on Gram-positive bacterial strains have been evidenced whereas RuOH remained non active.

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