Dual action of dipyridothiazine and quinobenzothiazine derivatives : anticancer and cholinesterase-inhibiting activity

The inverse correlation observed between Alzheimer’s disease (AD) and cancer has prompted us to look for cholinesterase-inhibiting activity in phenothiazine derivatives that possess anticancer properties. With the use of in silico and in vitro screening methods, our study found a new biological activity in anticancer polycyclic, tricyclic, and tetracyclic compounds. The virtual screening of a library of 120 ligands, which are the derivatives of azaphenothiazine, led to the identification of 25 compounds that can act as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Biological assays revealed the presence of selective inhibitors of eeAChE (electric eel AChE) or eqBuChE (equine serum BuChE) and nonselective inhibitors of both enzymes among the tested compounds. Their potencies against eeAChE were in a submicromolar-to-micromolar range with $IC_{50}$ values from 0.78 to 19.32 $\mu$M, while their $IC_{50}$ values against eqBuChE ranged from 0.46 to 10.38 $\mu$M. The most potent among the compounds tested was the tetracyclic derivative, 6-(4-diethylaminobut-2-ynyl)-9-methylthioquinobenzothiazine 24, which was capable of inhibiting both enzymes. 9-Fluoro-6-(1-piperidylethyl)quinobenzothiazine 23 was found to act as a selective inhibitor of eqBuChE with an $IC_{50}$ value of 0.46 $\mu$M. Compounds with such a dual antitumor and cholinesterase-inhibitory activity can be considered as a valuable combination for the treatment of both cancer and AD prevention. The results presented in this study might open new directions of research on the group of tricyclic phenothiazine derivatives

Salinity matters the most: How environmental factors shape the diversity and structure of cyanobacterial mat communities in high altitude arid ecosystems

IntroductionMicrobial mats are complex communities of benthic microorganisms that occur at the soil-water interphase in lakes’ shores, streams, and ponds. In the cold, mountainous desert of Eastern Pamir (Tajikistan), where scarce water bodies are influenced by extreme environmental conditions, photosynthetic cyanobacteria form diverse mats. The mats are characterized by different morphology and thickness. Their habitats exhibit a wide range of conditions; from oligosaline to hypersaline, oligotrophic to hypertrophic, and from cold ponds to hot springs. The aim of the present study was to reveal the taxonomic composition and structure of these mats and to examine which environmental factors influence them.MethodsFifty-one mats were collected from small water bodies around Bulunkul, Karakul, and Rangkul Lakes in 2015 and 2017. The physical and chemical properties of the water were measured in situ, while the concentration of nutrients was analyzed ex-situ. To reveal the taxonomic composition of the mats, the hypervariable V3-V4 region of the 16S rRNA gene was examined using NGS technology.ResultsThe results of bioinformatic analyses were compared with microscopic observations. They showed that Cyanobacteria was the dominant phylum, constituting on average 35% of bacterial ASVs, followed by Proteobacteria (28%), Bacteroidota (11%), and Firmicutes (9%). Synechococcales, Oscillatoriales, and Nostocales orders prevailed in Oxyphotobacteria, with a low contribution of Chroococcales, Gloeobacterales, and Chroococcidiopsidales. Occasionally the non-photosynthetic Vampirivibrionia (Melainabacteria) and Sericytochromatia from sister clades to Oxyphotobacteria were noted in the samples. Moreover, there was a high percentage of unidentified cyanobacterial sequences, as well as the recently described Hillbrichtia pamiria gen. et sp. nov., present in one of the samples. Salinity, followed by Na and K concentrations, correlated positively with the composition and structure of Oxyphotobacteria on different taxonomic levels and the abundance of all bacterial ASVs.DiscussionThe study suggests that the investigated communities possibly host more novel and endemic species. Among the environmental factors, salinity influenced the Oxyphotobacteria communities the most. Overall, the microenvironmental factors, i.e. the conditions in each of the reservoirs seemed to have a larger impact on the diversity of microbial mats in Pamir than the “subregional” factors, related to altitude, mean annual air temperature and distance between these subregions

Tracing ephemeral human occupation through archaeological, palaeoenvironmental and molecular proxies at Łabajowa Cave

Confirming ephemeral human occupation is a crucial issue in cave archaeology. The project ‘Tracing human presence in caves of Polish Jura’ focuses on the application of molecular methods to decode the history of past human activities in cave sediments in the Kraków-Częstochowa Upland. The results will be compared with archaeological and palaeoecological proxies

Long-term fire effects of the drained open fen on organic soils

Fire has considerable impact on vegetation and organic soils properties. As we observed that the differences between vegetation of burnt and unburnt areas on the rich fen are visible 11 years after the fire, we assumed that the post-fire changes are long lasting, yet limited exclusively to the burnt areas. In order to check this hypothesis we studied spatial differentiation of physical and chemical properties of soils, and productivity capacities of burnt and unburnt areas in the fen in Biebrza National Park. We took soil samples from the neighboring burnt and unburnt areas, from the depth of 0–30 cm and 30–50 cm. We analyzed 21 parameters of the soils including: pH, ash content, moisture, bulk density, exchangeable K, Na, Ca, available P, N-NH4+, N-NO3−, total N, C, K, Na, Ca, Mg, Fe, P; and calculated C:N, C:P ratios. Surface layer of the burnt soils differed significantly from the unburnt soils in respect of 17 out of 21 parameters. The most pronounced difference was observed for available phosphorous (on average 6 times higher for the burnt soils). The differences in the deeper layer were mostly insignificant. The burnt areas were also characterized by twofold higher plant productivity than recorded for the unburnt areas. The influence of fire on peaty soils was long lasting but mostly limited to the surface layer of the soils. In the case of particular soil features, the post-fire differences were modified by advanced muck formation (moorshing) processes in the unburnt areas. Since the fire led to long lasting increase of fertility, the recovery of fen vegetation is unlikely

Age and Land Use as Factors Differentiating Hydrochemistry and Plant Cover of Astatic Ponds in Post-Agricultural Landscape

Small, astatic ponds are important features of post-glacial landscape, which support heterogeneity and biodiversity of agricultural areas. In the presented research we explored differences in hydrochemistry and plant cover of 20 small ponds located in Northeastern Poland, characterized by diverse age and developed in differently managed areas. According to our research, though changes in water level are under direct influence of water balance in the catchment, to which belonged the ponds, their hydrochemistry seemed to be shaped by processes at the level lower than the catchment scale. Age of the ponds appeared to be an important factor influencing density and species composition of vegetation developed on the studied ponds

Surge-type Uisu glacier and its undisturbed forefield relief, Eastern Pamir, Tajikistan

The surge-type Uisu glacier and its forefield in the Tajik part of Eastern Pamir are described. To this end, 1977–2019 Landsat satellite imagery, the DEM, and a high-resolution orthophotomap were used, and detailed geomorphological mapping was carried out. The results show that the present-day position of the terminus of the studied glacier results from a surge that occurred before 1947. Currently, the glacier is losing mass. However, despite the visible characteristics of its thawing, the extent of the terminal zone has remained stable for several decades. Outside the glacier, there are no glacial landforms. This indicates that advances of surging glaciers may not create any surge-diagnostic features in their forefields. On the other hand, the genesis and interactions of landforms can reveal glacier surge, even in the absence of terminal and lateral glacial landforms

Colonization of decomposing Sphagnum moss litter by mycorrhizal roots in two types of peatland ecosystems

During a 35-month study on the decomposition of Sphagnum moss litter in poor fen and pine bog forest, an intensive colonization of litter-bags by mycorrhizal roots was observed during the decomposition process. Content of mycorrhizal roots in litter-bags, expressed as % mass of roots, was generally increasing during the decomposition in pine bog forest, and fluctuating during decomposition on poor fen, although in both cases the results were statistically insignificant. Two morphotypes of ericoid roots and two morphotypes of ectomycorrhizal roots were recorded from litter-bags on poor fen during the decomposition experiment, while in pine bog forest one morphotype of ericoid and nine morphotypes of ectomycorrhizal roots were recorded. Molecular identification of mycorrhizal roots succeeded only in the case of one ericoid and six putatively ectomycorrhizal morphotypes. Most morphotypes were recorded only once during the whole 35-month decomposition period, and only one ericoid and one ectomycorrhizal morphotypes were shared between the poor fen and pine bog forest communitiesPodczas blisko trzyletnich badań nad rozkładem mchu torfowca na torfowisku przejściowym oraz w borze bagiennym w północno-wschodniej Polsce zaobserwowano kolonizację materiału roślinnego w woreczkach ściółkowych przez silnie zmykoryzowane korzenie. Procentowa zawartość tych korzeni, wyrażona jako stosunek ich suchej masy do suchej masy rozkładających się szczątków roślinnych, generalnie zwiększała się wraz z upływem czasu w borze bagiennym, natomiast w przypadku torfowiska przejściowego nie wykazała wyraźnych tendencji; z racji niewielkiej liczby powtórzeń zaobserwowane różnice nie były jednak istotne statystycznie. W materiale roślinnym rozkładającym się na torfowisku przejściowym odnotowano obecność dwóch morfotypów korzeni wrzosowatych oraz dwóch morfotypów korzeni ektomykoryzowych, natomiast w borze bagiennym odnotowano jeden morfotyp korzeni wrzosowatych i 9 morfotypów korzeni ektomykoryzowych. Tylko jeden morfotyp wrzosowatych i jeden ektomykoryzowy były odnotowane w obu typach siedlisk; różnice wynikały z zasadniczych różnic w składzie zbiorowisk roślinnych pomiędzy badanymi powierzchniami. Większość (7 z 10) morfotypów ektomykoryz pojawiła się tylko raz podczas całego okresu trwania eksperymentu. Badania molekularne uzyskanych morfotypów powiodły się jedynie w siedmiu przypadkach: zidentyfikowano jeden gatunek tworzący mykoryzę erikoidalną, trzy gatunki tworzące ektomykoryzy (w tym jeden tworzący dwa morfotypy) oraz dwa gatunki grzybów wielkoowocnikowych znanych jako saprotrofy, prawdopodobnie wtórnie infekujących korzenie. Sekwencje uzyskane z pozostałych badanych morfotypów należały do grzybów mikroskopijnych najprawdopodobniej kolonizujących korzenie jako saprotrofy lub endofity. Pomimo że badania niniejsze stanowią jedynie szkicowe studium, to jednoznacznie wskazują na możliwość udziału grzybów mykoryzowych w procesach rozkładu materii roślinnej w ekosystemach torfowiskowych