Synthesis of anionic phthalocyanines as potential photodynamic active photosensitizers

Univerzita Karlova, Farmaceutická fakulta v Hradci Králové Katedra: Katedra farmaceutické chemie a farmaceutické analýzy Kandidát: Mgr. Jan Kollár Školitel: prof. PharmDr. Petr Zimčík, Ph.D. Konzultant: doc. PharmDr. Veronika Nováková, Ph.D. Disertační práce: Syntéza anionických derivátů ftalocyaninů jako potenciálních fotodynamicky aktivních látek Ftalocyaniny (Pc) a jejich aza-analogy (např. tetrapyrazinoporfyraziny TPyzPz) představují nadějnou skupinu organických barviv se zajímavými fotofyzikálními vlastnostmi (silná absorpce v oblasti 650-750 nm, vysoká produkce singletového kyslíku) velmi vhodnými pro použití ve fotodynamické terapii (PDT) nádorových onemocnění. Mají však také některé nevýhody snižující jejich potenciální použití v PDT (nízká rozpustnost ve vodě, silná tendence k agregaci). Téma mé disertační práce úzce navazuje na téma mé diplomové práce, během které byl připraven TPyzPz s 16 karboxylátovými skupinami v rigidním uspořádání, u kterého jsme pozorovali výrazný negativní vliv pH a sérových proteinů na fotodynamickou aktivitu. V první části disertační práce jsem proto připravil nový zinečnatý TPyzPz s 8 sulfonátovými skupinami na periferii charakterizovaný dobrou rozpustností ve vodě. Sulfonové kyseliny byly vybrány jako silnější kyseliny než karboxylové, takže se očekávalo, že...Charles University, Faculty of Pharmacy in Hradec Kralove Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Mgr. Jan Kollar Supervisor: prof. PharmDr. Petr Zimcik, Ph.D. Advisor: doc. PharmDr. Veronika Novakova, Ph.D. Doctoral Thesis: Synthesis of anionic phthalocyanines as potential photodynamic active photosensitizers Phthalocyanines (Pcs) and their aza-analogues (e.g. tetrapyrazinoporphyrazines, TPyzPzs) represent a promising group of organic dyes with interesting photophysical properties (strong absorption in area 650-750 nm, strong singlet oxygen production) highly suitable for the use in photodynamic therapy (PDT) of cancer. However, they have also some drawbacks lowering their potential use in PDT (low solubility in water, strong tendency to aggregate). The topic of my dissertation thesis closely follows the topic of my diploma thesis, during which TPyzPz with sixteen carboxylate groups in rigid arrangement was prepared and in which we have disclosed strong negative effect of low pH and serum proteins on photodynamic activity. In the first part of this thesis I prepared new zinc TPyzPz with eight sulfonate groups on periphery, which was characterised by good solubility in water. Sulfonates were chosen as stronger acids than carboxylic groups, so they were...Katedra farmaceutické chemie a farmaceutické analýzyDepartment of Pharmaceutical Chemistry and Pharmaceutical AnalysisFarmaceutická fakulta v Hradci KrálovéFaculty of Pharmacy in Hradec Králov

Synthesis of anionic phthalocyanines as potential photodynamic active photosensitizers

Univerzita Karlova, Farmaceutická fakulta v Hradci Králové Katedra: Katedra farmaceutické chemie a farmaceutické analýzy Kandidát: Mgr. Jan Kollár Školitel: prof. PharmDr. Petr Zimčík, Ph.D. Konzultant: doc. PharmDr. Veronika Nováková, Ph.D. Disertační práce: Syntéza anionických derivátů ftalocyaninů jako potenciálních fotodynamicky aktivních látek Ftalocyaniny (Pc) a jejich aza-analogy (např. tetrapyrazinoporfyraziny TPyzPz) představují nadějnou skupinu organických barviv se zajímavými fotofyzikálními vlastnostmi (silná absorpce v oblasti 650-750 nm, vysoká produkce singletového kyslíku) velmi vhodnými pro použití ve fotodynamické terapii (PDT) nádorových onemocnění. Mají však také některé nevýhody snižující jejich potenciální použití v PDT (nízká rozpustnost ve vodě, silná tendence k agregaci). Téma mé disertační práce úzce navazuje na téma mé diplomové práce, během které byl připraven TPyzPz s 16 karboxylátovými skupinami v rigidním uspořádání, u kterého jsme pozorovali výrazný negativní vliv pH a sérových proteinů na fotodynamickou aktivitu. V první části disertační práce jsem proto připravil nový zinečnatý TPyzPz s 8 sulfonátovými skupinami na periferii charakterizovaný dobrou rozpustností ve vodě. Sulfonové kyseliny byly vybrány jako silnější kyseliny než karboxylové, takže se očekávalo, že...Charles University, Faculty of Pharmacy in Hradec Kralove Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Mgr. Jan Kollar Supervisor: prof. PharmDr. Petr Zimcik, Ph.D. Advisor: doc. PharmDr. Veronika Novakova, Ph.D. Doctoral Thesis: Synthesis of anionic phthalocyanines as potential photodynamic active photosensitizers Phthalocyanines (Pcs) and their aza-analogues (e.g. tetrapyrazinoporphyrazines, TPyzPzs) represent a promising group of organic dyes with interesting photophysical properties (strong absorption in area 650-750 nm, strong singlet oxygen production) highly suitable for the use in photodynamic therapy (PDT) of cancer. However, they have also some drawbacks lowering their potential use in PDT (low solubility in water, strong tendency to aggregate). The topic of my dissertation thesis closely follows the topic of my diploma thesis, during which TPyzPz with sixteen carboxylate groups in rigid arrangement was prepared and in which we have disclosed strong negative effect of low pH and serum proteins on photodynamic activity. In the first part of this thesis I prepared new zinc TPyzPz with eight sulfonate groups on periphery, which was characterised by good solubility in water. Sulfonates were chosen as stronger acids than carboxylic groups, so they were...Katedra farmaceutické chemie a farmaceutické analýzyDepartment of Pharmaceutical Chemistry and Pharmaceutical AnalysisFarmaceutická fakulta v Hradci KrálovéFaculty of Pharmacy in Hradec Králov

On-line marketing communication

Obsah této bakalářské práce se zabývá marketingovou komunikací obchodů EXE Jeans. Tyto obchody prodávají smíšené zboží od více značek a jsou rozšířeny v oblasti celé České republiky. V první části práce jsou pokryty a vysvětleny teoretické pojmy úzce spjaty se zadaným tématem. V druhé, praktické části se pak dále zaměřuji na analýzu současného stavu vybrané společnosti, jejího prostředí a možných zlepšení v návrhové části, které jsou hlavním cílem této práce.This bachelor thesis focuses on marketing communication of EXE Jeans shop which is a retail store with many branches over Czech Republic. In the first part, there will be covered and explained theoretical foundations which are closely connected to the topic that I am working on and the second, practical part furthermore includes analysis of the current state in the selected company, its environment, and possible improvements in recommendations part which are the main objective.

Bioactivity of Methoxylated and Methylated 1-Hydroxynaphthalene-2-Carboxanilides: Comparative Molecular Surface Analysis

A series of twenty-six methoxylated and methylated N-aryl-1-hydroxynaphthalene- 2-carboxanilides was prepared and characterized as potential anti-invasive agents. The molecular structure of N-(2,5-dimethylphenyl)-1-hydroxynaphthalene-2-carboxamide as a model compound was determined by single-crystal X-ray di raction. All the analysed compounds were tested against the reference strain Staphylococcus aureus and three clinical isolates of methicillin-resistant S. aureus as well as against Mycobacterium tuberculosis and M. kansasii. In addition, the inhibitory profile of photosynthetic electron transport in spinach (Spinacia oleracea L.) chloroplasts was specified. In vitro cytotoxicity of the most e ective compounds was tested on the human monocytic leukaemia THP-1 cell line. The activities of N-(3,5-dimethylphenyl)-, N-(3-fluoro-5-methoxy-phenyl)- and N-(3,5-dimethoxyphenyl)-1-hydroxynaphthalene-2-carbox- amide were comparable with or even better than the commonly used standards ampicillin and isoniazid. All promising compounds did not show any cytotoxic e ect at the concentration >30 M. Moreover, an in silico evaluation of clogP features was performed for the entire set of the carboxamides using a range of software lipophilicity predictors, and cross-comparison with the experimentally determined lipophilicity (log k), in consensus lipophilicity estimation, was conducted as well. Principal component analysis was employed to illustrate noticeable variations with respect to the molecular lipophilicity (theoretical/experimental) and rule-of-five violations. Additionally, ligand-oriented studies for the assessment of the three-dimensional quantitative structure–activity relationship profile were carried out with the comparative molecular surface analysis to determine electron and/or steric factors that potentially contribute to the biological activities of the investigated compounds

Synthesis and Biological Evaluation of 2-Hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(Alkoxycarbonyl)amino]benzoates

A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport

The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood

BackgroundGenetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most frequently mutated autosomal recessive gene in FSGS is NPHS2. In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients.MethodsA representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the NPHS2 gene. The histological classification of FSGS followed the Columbia classification.ResultsWe detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2-associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years.ConclusionsWe identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the NPHS2-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world\u27s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

On-line marketing communication

Obsah této bakalářské práce se zabývá marketingovou komunikací obchodů EXE Jeans. Tyto obchody prodávají smíšené zboží od více značek a jsou rozšířeny v oblasti celé České republiky. V první části práce jsou pokryty a vysvětleny teoretické pojmy úzce spjaty se zadaným tématem. V druhé, praktické části se pak dále zaměřuji na analýzu současného stavu vybrané společnosti, jejího prostředí a možných zlepšení v návrhové části, které jsou hlavním cílem této práce

Synthesis of anionic phthalocyanines as potential photodynamic active photosensitizers

Charles University, Faculty of Pharmacy in Hradec Kralove Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Author: Mgr. Jan Kollar Supervisor: prof. PharmDr. Petr Zimcik, Ph.D. Advisor: doc. PharmDr. Veronika Novakova, Ph.D. Doctoral Thesis: Synthesis of anionic phthalocyanines as potential photodynamic active photosensitizers Phthalocyanines (Pcs) and their aza-analogues (e.g. tetrapyrazinoporphyrazines, TPyzPzs) represent a promising group of organic dyes with interesting photophysical properties (strong absorption in area 650-750 nm, strong singlet oxygen production) highly suitable for the use in photodynamic therapy (PDT) of cancer. However, they have also some drawbacks lowering their potential use in PDT (low solubility in water, strong tendency to aggregate). The topic of my dissertation thesis closely follows the topic of my diploma thesis, during which TPyzPz with sixteen carboxylate groups in rigid arrangement was prepared and in which we have disclosed strong negative effect of low pH and serum proteins on photodynamic activity. In the first part of this thesis I prepared new zinc TPyzPz with eight sulfonate groups on periphery, which was characterised by good solubility in water. Sulfonates were chosen as stronger acids than carboxylic groups, so they were..