RESUMO
In this manuscript, we report the photo-inactivation evaluation of new tetra-cationic porphyrins with peripheral Pt(II) complexes ate meta N-pyridyl positions in the antimicrobial photodynamic therapy (aPDT) of rapidly growing mycobacterial strains (RGM). Four different metalloderivatives were synthetized and applied. aPDT experiments in the strains of Mycobacteroides abscessus subsp. Abscessus (ATCC 19977), Mycolicibacterium fortuitum (ATCC 6841), Mycobacteroides abscessus subsp. Massiliense (ATCC 48898), and Mycolicibacterium smegmatis (ATCC 700084) conducted with adequate concentration of photosensitizers (PS) under white-light conditions at 90 min (irradiance of 50 mW cm-2 and a total light dosage of 270 J cm-2) showed that the Zn(II) derivative is the most effective PS significantly reduced the concentration of viable mycobacteria. The effectiveness of the molecule as PS for PDI studies is also clear with mycobacteria, which is strongly related with the porphyrin peripheral charge and coordination platinum(II) compounds and consequently about the presence of metal center ion. This class of PS may be promising antimycobacterial aPDT agents with potential applications in medical clinical cases and bioremediation.
Assuntos
Mycobacterium , Porfirinas , Platina/farmacologia , Luz , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , AntibacterianosRESUMO
We report the photoinactivation evaluation of Ag(II) porphyrins (cationic AgTMeP and anionic AgTPPS) in the antimicrobial photodynamic therapy (aPDT) of rapidly growing mycobacterial strains. The aPDT assays in the Mycolicibacterium fortuitum, Mycobacteroides abscessus subs. abscessus, Mycobacteroides abscessus subsp. massiliense, and Mycolicibacterium smegmatis strains conducted without aggregating photosensitizers (PS) under irradiation for 90 min (270 J/cm2) showed that the most effective PS (nanomolar range) significantly reduced the concentration of viable mycobacteria. Structural damage on the Mycolicibacterium smegmatis non-pathogenic model was observed using atomic force microscopy, revealing that Ag(II)-porphyrin induced extensive changes in its electrical and adhesive forces, demonstrating changes in topography that may be linked to the action of different fractions of reactive oxygen species. The results presented in this paper provide solid evidence for using cationic porphyrin AgTMeP as an alternative to the conventional treatment of cutaneous mycobacteriosis and the disinfection of prosthetic devices and hospital equipment.
Assuntos
Anti-Infecciosos , Mycobacterium , Fotoquimioterapia , Porfirinas , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Cátions/química , Cátions/farmacologia , Micobactérias não Tuberculosas , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Prata/farmacologiaRESUMO
Achyrocline flaccida aqueous extract was obtained by macerating wildflowers. The phytochemical profile present in the A. flaccida aqueous extract was elucidated by HPLC-ESI-MS/MS. Toxicity was evaluated in vitro by comet assay in peripheral blood mononuclear cells (PBMCs) and in vivo using Caenorhabditis elegans as a model. The antioxidant activity was also evaluated, and antimycobacterial activity was assessed by the broth microdilution method. The compounds present in the aqueous extract mainly belonged to the flavonoid class (89%). The concentrations that showed protective effects in C. elegans against oxidative stress and antimycobacterial activity had no toxic effects. The antimycobacterial activity test demonstrated that the concentration of 1,560 µg mL-1 inhibited the growth and eradication of the mycobacterial tested strains. Based on our findings, the A. flaccida aqueous extract presents a viable potential in developing new phytotherapeutic drugs against mycobacteria of clinical relevance.
Assuntos
Achyrocline , Asteraceae , Achyrocline/química , Animais , Antibacterianos/farmacologia , Antioxidantes/química , Asteraceae/química , Brasil , Caenorhabditis elegans , Leucócitos Mononucleares , Extratos Vegetais/química , Espectrometria de Massas em TandemRESUMO
This study investigated the chemical constituents of Gaultheria procumbens essential oil and is the first to relate cytogenotoxicity with oxidative metabolism and antimicrobial activity. Chromatographic analysis of the essential oil showed methyl salicylate (99.96%) and linalool (0.04%) as the major compounds. The essential oil showed no signs of cytogenotoxicity at different concentrations (1.82 to 58.34 mg mL-1). Furthermore, G. procumbens essential oil and methyl salicylate were used to evaluate the minimal inhibitory concentrations (MIC) and minimal microbicidal concentrations (MMC). The results showed efficacy against several microorganisms, including Aeromonas caviae, Candida albicans, and Mycobacterium fortuitum with MIC values ranging from 1.82 to 3.64 mg mL-1 and MMC values ranging from 3.64 to 12.67 mg mL-1, which were confirmed by time-kill kinetics. Based on our results, the essential oil is a promising alternative to developing future formulations to treat infections caused by microorganisms.
Assuntos
Anti-Infecciosos , Óleos Voláteis , Anti-Infecciosos/farmacologia , Candida albicans , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Compostos Fitoquímicos/farmacologiaRESUMO
Using molecular hybridization, specific sulfonamide derivatives of eugenol were synthesized with subtle modifications in the allylic chain of the eugenol subunit (and also in the nature of the substituent group in the sulfonamide aromatic ring) which allowed us to study the influence of structural changes on the antimicrobial potential of the hybrids. Antimicrobial test results showed that most of the synthesized hybrid compounds showed good activity with better results than the parent compounds. Molecular docking studies of the hybrids with the essential bacterial enzyme DHPS showed complexes with low binding energies, suggesting that DHPS could be a possible target for the antibacterial sulfonamide-eugenol hybrids. Furthermore, most of the final compounds presented similar docking poses to that of the crystallographic ligand sulfamethoxazole. The results obtained allow us to conclude that these are promising compounds for use as new leads in the search for new antibacterial sulfonamides.
Assuntos
Antibacterianos/farmacologia , Desenho de Fármacos , Eugenol/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Sulfonamidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Eugenol/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/químicaRESUMO
Rapidly growing mycobacteria (RGM) are found in non-sterile water and often associated with severe post-surgical infections and affect immunocompromised patients. In addition, RGM can prevent the host's immune response and have the ability to adhere to and form biofilms on biological and synthetic substrates, making pharmacological treatment difficult because conventional antimicrobials are ineffective against biofilms. Thus, there is an urgent need for new antimicrobial compounds that can overcome these problems. In this context, sulfonamides complexed with Au, Cd, Ag, Cu, and Hg have shown excellent activity against various microorganisms. Considering the importance of combating RGM-associated infections, this study aimed to evaluate the activity of sulfonamide metal complexes against RGM biofilm. The sulfonamides were tested individually for their ability to inhibit mycobacterial formation and destroy the preformed biofilm of standard RGM strains, such as Mycobacterium abscessus, M. fortuitum, and M. massiliense. All sulfonamides complexed with metals could reduce, at subinhibitory concentrations, the adhesion and biofilm formation of three RGM species in polystyrene tubes. It is plausible that the anti-biofilm capacity of the compounds is due to the inhibition of c-di-GMP synthesis, which is an important signal for RGM biofilm formation. Hence, the impacts and scientific contribution of this study are based on the discovery of a potential new therapeutic option against RGM-associated biofilm infections. Sulfonamides complexed with metals have proven to be a useful and promising tool to reduce microbial adhesion on inert surfaces, stimulating the improvement of methodologies to insert compounds as new antibacterial and coating agents for medical and hospital materials.
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Achyrocline flaccida (Weinm) DC. essential oil was obtained by hydrodistillation of wild flowers from southern Brazil. We explored, for the first time, the phytochemical composition, toxicity, resistance to oxidative stress in Caenorhabditis elegans, and antimycobacterial activities of A. flaccida essential oil. Twenty-four compounds were identified by GC-FID-MS and the major constituents identified were α-pinene (41.10%) and caryophyllene (30.52%). The essential oil showed no signs of genotoxicity in the comet assay and presented relevant antioxidant capacity since it prevented ROS production in the C. elegans model. Furthermore, the minimal inhibitory concentrations (MIC) results showed that M. abscessus, M. massiliense, and M. fortuitum had their growth inhibited by A. flaccida essential oil. Therefore, the essential oil of this plant is a promising alternative in the search for new compounds capable of decreasing oxidative stress and treating mycobacteriosis.
Assuntos
Achyrocline , Óleos Voláteis , Animais , Brasil , Caenorhabditis elegans , Óleos Voláteis/farmacologia , Compostos Fitoquímicos/farmacologiaRESUMO
Rapidly growing mycobacteria (RGM) are pathogens that belong to the mycobacteriaceae family and responsible for causing mycobacterioses, which are infections of opportunistic nature and with increasing incidence rates in the world population. This work evaluated the use of six water-soluble cationic porphyrins as photosensitizers for the antimicrobial photodynamic therapy (aPDT) of four RGM strains: Mycolicibacterium fortuitum, Mycolicibacterium smeagmatis, Mycobacteroides abscessus subs. Abscessus, and Mycobacteroides abscessus subsp. massiliense. Experiments were conducted with an adequate concentration of photosensitizer under white-light irradiation conditions over 90 min and the results showed that porphyrins 1 and 2 (M = 2H or ZnII ion) were the most effective and significantly reduced the concentration of viable mycobacteria. The present work shows the result is dependent on the metal-center ion coordinated in the cationic porphyrin core. Moreover, we showed by atomic force microscopy (AFM) the possible membrane photodamage caused by reactive oxygen species and analyzed the morphology and adhesive force properties. Tetra-positively charged and water-soluble metalloporphyrins may be promising antimycobacterial aPDT agents with potential applications in medical clinical cases and bioremediation.
Assuntos
Complexos de Coordenação/farmacologia , Metais Pesados/farmacologia , Mycobacterium/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Cátions/química , Cátions/farmacologia , Complexos de Coordenação/química , Metais Pesados/química , Estrutura Molecular , Mycobacterium/crescimento & desenvolvimento , Processos Fotoquímicos , Fármacos Fotossensibilizantes/química , Porfirinas/química , Solubilidade , Água/químicaRESUMO
In this manuscript, we report, for the first time, the photoinactivation evaluation of tetra-cationic porphyrins with peripheral Pt (II)-bpy complexes in the photodynamic inactivation (PDI) of rapidly growing mycobacterial strains (RGM). Two different isomeric Pt (II)-porphyrins were synthetized and applied. PDI experiments in the strains of Mycobacteroides abscessus subsp. Abscessus (ATCC 19977), Mycolicibacterium fortuitum (ATCC 6841), Mycobacteroides abscessus subsp. Massiliense (ATCC 48898), and Mycolicibacterium smegmatis (ATCC 700084) conducted with adequate concentration (without aggregation) of photosensitizers (PS) under white-light illumination for 90 min showed that the most effective PS significantly reduced the concentration of viable mycobacteria. The present results show that positively charged porphyrins at the meta position (3-PtTPyP) are more efficient PS against M. abscessus, M. fortuitum, M. massiliense, and M. smegmatis. The effectiveness of the molecule as PS for PDI studies is also clear with mycobacteria, which is strongly related with the porphyrin peripheral charge and coordination platinum (II) compounds and consequently their solubility in physiological media. Tetra-cationic PS may be promising anti-mycobacterial PDI agents with potential applications in medical clinical cases and bioremediation.
Assuntos
Mycobacterium , Porfirinas , Cátions , Luz , Fármacos Fotossensibilizantes/farmacologiaRESUMO
This manuscript reports, at the first time, the photoinactivation evaluation of tetra-cationic and anionic porphyrins as photosensitizers (PS) for the photodynamic inactivation (PDI) of rapidly growing mycobacteria strains. Two different charged porphyrin groups were obtained commercially. PDI experiments in the strains Mycobacterium massiliense e Mycobacterium fortuitum conducted with adequate concentration (without aggregation) of photosensitizer under white light at a fluence rate of 50â¯mW/cm2 over 90â¯min showed that the most effective PS caused a 100 times reduction in the concentration of viable mycobacteria. The present results show that porphyrin with positively charge are more efficient PS than anionic porphyrin (negatively charged) against M. massiliense e M. fortuitum. It is also clear that the effectiveness of the molecule as PS for PDI studies with mycobacteria is strongly related with the porphyrin peripheral charge, and consequently their solubility in physiological media. Cationic PSs might be promising anti-mycobacteria PDI agents with potential applications in medical clinical cases and bioremediation.