Photophysical, photobiological, and mycobacteria photo-inactivation properties of new meso-tetra-cationic platinum(II) metalloderivatives at meta position.

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.

Photodynamic inactivation of different Candida species and inhibition of biofilm formation induced by water-soluble porphyrins.

BACKGROUND: Candida spp. is the main fungal genus related to infections in humans, and its treatment has become a challenge due to the production of biofilm and its resistance/multi-resistance profile to conventional antifungals. Antimicrobial photodynamic therapy stands out as a treatment characterized by a broad spectrum of antimicrobial action, being able to induce oxidative stress in pathogens, and porphyrins are photosensitizers with high selectivity to pathogens. Thus, this work aimed to analyze the photoinactivation of different species of Candida by two cationic (4-H2TMeP+ and 3-H2TMeP+) and one anionic (4-H2TPSP‒) porphyrins. MATERIALS AND METHODS: Microdilution assays were performed to determine the MIC100, with subsequent determination of MFC100. Determination of oxidative species was done through the use of scavengers, while biofilm morphological features were investigated using the atomic force microscopy. RESULTS: Cationic porphyrins were significantly efficient in inactivating Candida albicans and non-albicans species with 100% growth inhibition and fungicidal activity (MFC100/MIC100 ≤ 4.0). The cationic porphyrins were also able to interfere in Candida spp biofilm formation. The photo-oxidative mechanism activated by 3-H2TMeP+ in Candida spp. is concurrent with the production of singlet oxygen and oxygen radical species. In the AFM analysis, 3-H2TMeP+ was able to reduce yeast adhesion to the surface. CONCLUSIONS: Cationic porphyrins can photo-inactivate different species of Candida in both planktonic and biofilm-associated forms, and reduce the adhesion of these fungi to the surface.

Antibacterial, antifungal, and anti-biofilm effects of sulfamethoxazole-complexes against pulmonary infection agents.

Antibiotic resistance associated with pulmonary infection agents has become a public health problem, being considered one of the main priorities for immediate resolution. Thus, to increase the therapeutic options in the fight against resistant microorganisms, the synthesis of molecules from pre-existing drugs has shown to be a promising alternative. In this sense, the present work reports the synthesis, characterization, and biological evaluation (against fungal and bacterial agents that cause lung infections) of potential metallodrugs based on sulfamethoxazole complexed with AuI, AgI, HgII, CdII, NiII, and CuII. The minimal inhibitory concentration (MIC) value was used to evaluate the antifungal and antibacterial properties of the compounds. In addition, it was also evaluated the antibiofilm capacity in Pseudomonas aeruginosa, through the quantification of its biomass and visualization using atomic force microscopy. For each case, molecular docking calculations were carried out to suggest the possible biological target of the assayed inorganic complexes. Our results indicated that the novel inorganic complexes are better antibacterial and antifungal than the commercial antibiotic sulfamethoxazole, highlighting the AgI-complex, which was able to inhibit the growth of microorganisms that cause lung diseases with concentrations in the 2-8 µg mL-1 range, probably at targeting dihydropteroate synthetase - a key enzyme involved in the folate synthesis. Furthermore, sulfamethoxazole complexes were able to inhibit the formation of bacterial biofilms at significantly lower concentrations than free sulfamethoxazole, probably mainly targeting the active site of LysR-type transcriptional regulator (PqsR). Overall, the present study reports preliminary results that demonstrate the derivatization of sulfamethoxazole with transition metal cations to obtain potential metallodrugs with applications as antimicrobial and antifungal against pulmonary infections, being an alternative for drug-resistant strains.

Nanomolar effective report of tetra-cationic silver(II) porphyrins against non-tuberculous mycobacteria in antimicrobial photodynamic approaches.

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.

Photo-damage promoted by tetra-cationic palladium(II) porphyrins in rapidly growing mycobacteria.

Antimicrobial photodynamic therapy (aPDT) has gained prominence in microbiology, especially in treating non-invasive infections. Diseases such as mycobacteriosis, which causes localized infections and has a slow treatment, tend to be future targets for this type of technology. Therefore, this study aimed to explore the action of two isomeric Pd(II)-porphyrins on fast-growing mycobacterial strains (RGM). Tetra-cationic porphyrins (4-PdTPyP and 3-PdTPyP) were synthesized and applied against standard strains of Mycobacteroides abscessus subsp. abscessus (ATCC 19977), Mycolicibacterium fortuitum (ATCC 6841), Mycolicibacterium smegmatis (ATCC 700084), and Mycobacteroides abscessus subsp. massiliense (ATCC 48898). Reactive oxygen species (ROS) scavengers were used in an attempt to determine possible ROS produced by the photosensitizers (PS) under study. Moreover, the impact of porphyrin on the mycobacterial surface was further evaluated by atomic force microscopy (AFM), and we observed significant damage on cells walls and altered nanomechanical and electrostatic adhesion properties. The results presented herein show that the positively charged porphyrin at the meta position (3-PdTPyP) was the most efficient PS against the RGM strains, and its bactericidal activity was proven in two irradiation sessions, with singlet oxygen species being the main ROS involved in this process. This study demonstrated the therapeutic potential of porphyrins, especially the 3-PdTPyP derivative.

Molecular docking, quorum quenching effect, antibiofilm activity and safety profile of silver-complexed sulfonamide on Pseudomonas aeruginosa.

Microbial infections caused by sessile microorganisms are known to be a more challenging issue than infections caused by the same microorganisms in the planktonic state. Pseudomonas aeruginosa is an opportunistic pathogen and biofilm-forming agent. This species presents intense cellular communication mediated by signaling molecules. This process is known as quorum sensing (QS) and induces the transcription of specific genes that favors cell density growth and three-dimensional bacterial grouping. In this context, the discovery of compounds capable of inhibiting the action of the QS signaling molecules seems to be a promising strategy against biofilms. This work aimed to evaluate the anti-biofilm action and the in vitro safety profile of a sulfamethoxazole-Ag complex. The results obtained indicate potential anti-biofilm activity through QS inhibition. In silico tests showed that the compound acts on the las and pqs systems, which are the main regulators of biofilm formation in P. aeruginosa. Additionally, the molecule proved to be safe for human peripheral blood mononuclear cells.

Multifunctional coatings of exfoliated and reassembled graphite on cellulosic substrates.

Exfoliated and reassembled graphite (ERG) forms macroscopic, high aspect ratio (1 : >106) and highly conductive coating layers that are strongly adherent to paper, wood, cloth, ceramic and other substrates. The coating precursor is an aqueous dispersion of graphite that exfoliates spontaneously in alkaline cellulose solutions, forming stable dispersions. These can be applied to the substrates by using different painting, coating and lithography techniques. The coating morphology changes from highly smooth to porous and rough, depending on the finishing procedure used. Coated paper sheets are flexible and they perform as leads in electrical circuitry and as electrodes in electrodeposition, supercapacitors, hygroelectricity cells and other electrochemical devices suitable for flexible and wearable electronics. These unique properties of ERG are explained as a consequence of the amphiphilic character of cellulose, which allows it to play the roles of exfoliant, dispersant, stabilizer, adhesive and plasticizer, while graphite powder is transformed into a cohesive laminated nanocomposite.

Peripheral tetra-cationic Pt(II) porphyrins photo-inactivating rapidly growing mycobacteria: First application in mycobacteriology.

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.