There is an increasing need to discover effective methods for treating municipal wastewater and addressing the threat of multidrug-resistant (MDR) strains of bacteria spreading into the environment ...and drinking water. Photodynamic inactivation (PDI) that combines a photosensitiser and light in the presence of oxygen to generate singlet oxygen and other reactive species, which in turn react with a range of biomolecules, including the oxidation of bacterial genetic material, may be a way to stop the spread of antibiotic-resistant genes. The effect of 5,10,15,20-(pyridinium-3-yl)porphyrin tetrachloride (TMPyP3) without light, and after activation with violet-blue light (VBL) (394 nm; 20 mW/cm.sup.2 ), on MDR strains of Pseudomonas aeruginosa, Klebsiella pneumoniae and K. pneumoniae OXA-48 in tap water and municipal wastewater was investigated. High toxicity (~2 muM) of TMPyP3 was shown in the dark on both strains of K. pneumoniae in tap water, while on P. aeruginosa toxicity in the dark was low (50 muM) and the PDI effect was significant (1.562 muM). However, in wastewater, the toxicity of TMPyP3 without photoactivation was much lower (12.5-100 muM), and the PDI effect was significant for all three bacterial strains, already after 10 min of irradiation with VBL (1.562-6.25 muM). In the same concentrations, or even lower, an anti-adhesion effect was shown, suggesting the possibility of application in biofilm control. By studying the kinetics of photoinactivation, it was found that with 1,562 muM of TMPyP3 it is possible to achieve the complete destruction of all three bacteria after 60 min of irradiation with VBL. This study confirmed the importance of studying the impact of water constituents on the properties and PDI effect of the applied photosensitiser, as well as checking the sensitivity of targeted bacteria to light of a certain wavelength, in conditions as close as possible to those in the intended application, to adjust all parameters and perfect the method.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Opportunistic premise plumbing pathogens (OPPPs) form a group of microorganisms that normally live in water supply systems and have adapted especially well to the conditions in premise plumbing ...systems, and as such pose a threat to human health. Since the beginning of the 21st century, this threat has been escalating, and it is becoming increasingly evident that current water disinfection methods fall short in effectively controlling these pathogens. In researching new approaches to this emergency, phototherapy looks promising, especially one that combines photosensitizers, light, and oxygen, which is known as photodynamic inactivation (PDI). This review describes the main characteristics of the recognized (Pseudomonas aeruginosa, Legionella pneumophila, and Mycobacterium avium) and most important emerging OPPPs, and it offers a brief overview of current disinfection methods and their limitations in the fight against OPPPs. The principle and outcomes of PDI with endogenous and, in particular, exogenous photosensitizers are then explained and described through representative examples of PDI on recognized and emerging OPPPs and their biofilms. Finally, the prospects and future directions of PDI research in water disinfection and control of OPPPs are discussed.
Porphyrins are frequently employed in photodynamic therapy (PDT), a non-invasive technique primarily utilized to treat subcutaneous cancers, as photosensitizing agents (PAs). The development of a new ...PA with improved tissue selectivity and efficacy is crucial for expanding the application of PDT for the management of diverse cancers. We investigated the systemic effects of 5,10,15,20-tetrakis(N-methylpyridinium-3-yl)-porphyrin (TMPyP3) using Drosophila melanogaster adult males. We established the oral administration schedule and demonstrated that TMPyP3 was absorbed and stored higher in neuronal than in non-neuronal extracts. Twenty-four hours after oral TMPyP3 photoactivation, the quantity of hydrogen peroxide (H2O2) increased, but exclusively in the head extracts. Regardless of photoactivation, TMPyP3 resulted in a reduced concentration of H2O2 after 7 days, and this was linked with a decreased capacity to climb, as indicated by negative geotaxis. The findings imply that systemic TMPyP3 therapy may disrupt redox regulation, impairing cellular signaling and behavioral outcomes in the process. To determine the disruptive effect of porphyrins on redox homeostasis, its duration, and the mechanistic variations in retention across various tissues, more research is required.
A series of N‐methylated and N‐oxidised tripyridyl porphyrins were synthesised, characterised, and their PDT activity was studied with six cell lines. All the tested porphyrins with a long alkyl ...chain, except one, were more efficient for PDT than an N‐methylated hydrophilic porphyrin and N‐oxidised porphyrin without the long alkyl chain. Generally, N‐methylated tripyridyl porphyrins were more active than those N‐oxidised, but IC50 values for phototoxicity of two N‐oxides, named TOPyP3‐C17H33O and TOPyP3‐C17H35, were still in the nanomolar concentration range for most of the tested cell lines. However, TOPyP3‐C17H35 did not show phototoxicity on human foreskin fibroblast cells. Two methylated amphiphilic porphyrins, named TMPyP3‐C17H33 and TMPyP4‐C17H35, showed significant dark toxicity, whereas none of the oxidopyridyl porphyrins were toxic without light activation. The selected photosensitisers were shown to be apoptosis inducers, and had inhibitory effects on the clonogenic growth of HCT116 and HeLa cells. All three N‐methylated amphiphilic porphyrins significantly reduced the migratory potential of HCT116 cells. Porphyrins TMPyP3‐C17H35 and TOPyP3‐C17H35 reduced the activity of acid ceramidase, whereas TOPyP3‐C17H33O had a significant inhibitory effect on sphingosine kinase 1 activity in HeLa cells. Compounds with this dual activity were shown to be the most promising photosensitisers, with potential to treat invasive cancers.
A red light for cancer: With the aim of targeting sphingolipid metabolism for improved photodynamic therapy, N‐methylated and N‐oxidised tripyridyl porphyrins with long alkyl chains were shown to inhibit acid ceramidase and sphingosine kinase 1, and were efficient photosensitisers for the direct killing of cancer cells and the inhibition of clonogenic growth and migration. Thus, these compounds show potential to advance current treatment strategies for cancer patients.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The River Drava is one of the major, inexhaustible water sources not only for Croatia, but also for the other European countries it flows through. This study is based on the observations of 15 water ...variables at three sampling stations in the lower River Drava over a 24 year period. Although the obtained results revealed an improvement of most of the parameters, the values of some of them (i.e. NH4-N, NO3-N, BOD5, total coliform and heterotrophic bacteria) are still above the approved limits for water Class II. The results of principal component analysis (PCA) confirmed an existence of three clearly separated zones. The first zone corresponds to a rural upstream part of River Drava, which is characterised with low level pollution. The influences of untreated domestic waters become more noticeable in the second more densely populated suburban zone (II) located upstream of the city of Osijek. According to the results of the PCA, untreated wastewaters from Osijek are becoming contributing factors to the high pollution level of the river in the third (III) suburban zone. This study shows the usefulness of the PCA method for analysis and interpretation of complex data sets as well as for determination of pollution sources.
Two cationic porphyrins bearing an isothiocyanate group for conjugation to monocolonal antibodies have been synthesized. The two porphyrins conjugated efficiently to three monoclonal antibodies ...(anti-CD104, anti-CD146 and anti-CD326), which recognize antigens commonly over-expressed on a range of tumour cells. In vitro, all conjugates retained the phototoxicity of the porphyrin and the immunoreactivity of the antibody. Mechanistic studies showed that conjugates formed from the mono- and tri-cationic porphyrin and anti-CD104 antibody mediated apoptosis following irradiation with non-thermal red light of 630 ± 15 nm wavelength. In vivo antibody conjugates caused suppression of human LoVo tumour growth in immunodeficient NIH III mice, similar to the commercial photodynamic therapy (PDT) agent Photofrin®, but at administered photosensitizer doses that were more than two orders of magnitude lower. Positron emission tomography (PET) following PDT showed a large, early increase in uptake of ¹⁸fluorodeoxyglucose (FDG) by tumours treated with the anti-CD104 conjugates. This effect was not observed with Photofrin® or with conjugates formed from the same photosensitizers conjugated to an irrelevant antibody.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
New pyrrolo derivatives of benzo
bthiophene 1,1-dioxide have been synthesised via 1,3-dipolar cycloaddition reactions. Reaction of benzo
bthiophene 1,1-dioxide with stabilised azomethine ylides gave ...products in low yield but high stereoselectivity whereas reaction with non-stabilised azomethine ylides gave high overall yields but low stereoselectivity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A Cu(II)-rutin complex was prepared with a metal to ligand molar ratio of 3:2 by mixing stoichiometric amounts of rutin and CuCl2. The isolated complex was characterized by IR and UV/Vis spectroscopy ...and incorporated into a plasticized PVC-membrane using o-nitrophenyloctylether as a plasticizer (66% plasticizer, 33% PVC and 1% Cu(II)-rutin complex). The sensing characteristics of the membrane against Cu(II) ion were investigated using direct potentiometry. The membrane showed -4 a Nernstian response for Cu(II) ion with a slope of 28.5 mV/decade of activity between 5 x 10and 4-2 x 10M. The influence of several inorganic cations on the response of the Cu(II)-rutin complex based membrane was also investigated and the corresponding potentiometric selectivity coefficients were estimated and optimized with Solver (Excel).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The synthesis of three cationic 5,15-diphenyl porphyrins, bearing an isothiocyanate group for conjugation to proteins is described. The potential of these compounds as targeted photosensitisers for ...use in photodynamic therapy (PDT) is demonstrated by their efficient conjugation to monoclonal antibodies and the ability of the bioconjugates to bind and photodynamically inactivate cancer cells that express the corresponding antigen.
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