Synthesis, enzyme inhibition, and molecular docking studies of a novel chalcone series bearing benzothiazole scaffold.

This study reports the facile synthesis of a novel series of benzothiazole-chalcones, in addition to their inhibitory profile on important metabolic enzymes including human carbonic anhydrases (hCA-I, hCA-II) and paraoxonase (PON-1). The inhibition parameters, IC50 (concentration for 50% inhibition) and Ki (dissociation constant) values, toward the title enzymes were determined for the studied compounds. As a result, IC50 values of hydratase activity were in the range 4.15-5.47 and 2.56-4.58 µM for hCA-I and hCA-II, respectively. At the same time, IC50 values of esterase activity were in the range 24.91-104.00 and 35.25-97.00 µM, while Ki values were in the range 14.43-59.66 and 26.65-73.34 µM for hCA-I and hCA-II, respectively. In addition, PON-1 enzyme inhibition results showed interesting inhibitory effects, with IC50 values between 13.28 and 16.68 µM. Finally, a comprehensive approach was established for the synthesized compounds based on theoretical calculations, which have been done using B3LYP, PBE0 theories and SVP, TVZP, TVZPP basis sets, followed by docking studies by which the outputs proved the harmonically flows with the experimental results.

Synthesis, characterization, biochemical, and molecular modeling studies of carvacrol-based new thiosemicarbazide and 1,3,4-thiadiazole derivatives.

A series of carvacrol-based thiosemicarbazide (3a-e) and 1,3,4-thiadiazole-2-amine (4a-e) were designed and synthesized for the first time. The structures were characterized by nuclear magnetic resonance and high resolution mass spectroscopy techniques. All compounds were examined for some metabolic enzyme activities. Results indicated that all the synthetic molecules exhibited powerful inhibitory actions against human carbonic anhydrase I and II (hCAI and II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes compared to the standard molecules. Ki values of five novel thiosemicarbazides and five new 1,3,4-thiadiazole-2-amine derivatives (3a-e and 4a-e) for hCA I, hCA II, AChE, and BChE enzymes were obtained in the ranges 0.73-21.60, 0.42-15.08 µM, 3.48-81.48, 92.61-211.40 nM, respectively. After the experimental undertaking, an extensive molecular docking analysis was conducted to scrutinize the intricate details of interactions between the ligand and the enzyme in question. The principal focus of this investigation was to appraise the potency and efficacy of the most active compound. In this context, the calculated docking scores were noted to be remarkably low, with values of -8.65, -7.97, -8.92, and -8.32 kcal/mol being recorded for hCA I, hCA II, AChE, and BChE, respectively. These observations suggest a high affinity and specificity of the studied compounds toward the enzymes, as mentioned earlier, which may pave the way for novel therapeutic interventions aimed at modulating the activity of these enzymes.

Evaluation of Using Direct Viral Transport Medium Samples without Nucleic Acid Isolation for SARS-CoV-2 Diagnosis by RT-PCR.

BACKGROUND: Diagnosis with reverse transcriptase polymerase chain reaction (RT-PCR) test is a very important step for the control of the COVID-19 pandemic. The aim of this study is to compare the RT-PCR results of the samples taken directly from the viral transport medium (VTM) without extraction with the RT-PCR results of two different extraction methods, one automated and the other manual, in the diagnosis of COVID-19. METHODS: Among the respiratory tract samples sent to Sakarya Training and Research Hospital Microbiology Laboratory for COVID-PCR study, 20 negative and 43 positive samples with different cycle threshold (CT) values were included in the study. Both manual nucleic acid isolation with the vNAT isolation kit (Bioeksen, Turkey) and automatic nucleic acid isolation with the EZ1 Virus Mini Kit v2.0 in the isolation device were performed simulta-neously from the patient samples included in the study and the results were compared. RESULTS: The mean Ct values of the samples were found to be 21.58 using manual vNAT as the extraction method, 17.63 using the automated magnetic bead method, and 21.45 in PCR from direct VTM without extraction. When the automatic magnetic beads extraction method was taken as the reference method, the sensitivity of direct PCR was 97.3%, the specificity was 95%, the positive predictive value was 97.3%, and the negative predictive value was 95%. Phi coefficients were found to be 0.927 between vNAT and direct PCR, 1 between vNAT and EZ1, and 0.922 between direct PCR and EZ1. CONCLUSIONS: Direct PCR has advantages such as eliminating RNA extraction and purification steps, providing a shorter detection time, and using less labor and less consumables without reducing the diagnostic accuracy. It is thought that this method can help as a useful process management for the control of the epidemic in countries with limited resources.

Radiographic assessment of the response of teeth following trauma during screw placement for maxillo-mandibular fixation.

BACKGROUND/AIM: Maxillo-mandibular fixation (MMF) screws have gained popularity in recent years for inter-maxillary fixation. MMF screw application involves the risk of dental injury. However, knowledge about the healing responses after root damage in humans is limited, thereby warranting the need to classify the radiographic assessment of healing to enable better prediction of the healing response and effective management of the potential complications. The aim of this study was to assess and classify the radiographic assessment of the responses after root damage to evaluate the long-term outcomes. MATERIAL AND METHODS: The dental records of patients who underwent orthognathic surgery or trauma management during 2014-2016 at an Oral and Maxillofacial Surgery Department were retrospectively analyzed. The data regarding dental injuries resulting from MMF screw application were evaluated. In total, 16 patients with 34 roots damaged from MMF screw application were enrolled. Post-operative orthopantomographs were analyzed by visual inspection of the affected areas to clarify the extent of root healing. The inter- and intra-rater reliability assessments were subsequently performed. RESULTS: The results indicated substantial inter- and intra-rater reliability of the responses. Most cases of root damage that were not radiographically related to the pulp (Schulte-Geers Class III defects) had complete or partial healing responses. In addition, 20% of the defects related to the pulp had additional resorption of the bone/dental tissues during the follow-up period. CONCLUSIONS: Three different radiographic responses of root damage following MMF screw trauma were identified. Understanding these different responses is important to guide the management of the potential complications. This proposed radiographic assessment can be used to present root healing data in a more standardized and reliable manner.

Novel propanolamine derivatives attached to 2-metoxifenol moiety: Synthesis, characterization, biological properties, and molecular docking studies.

The synthesis of seven new ß-amino alcohols was designed and performed by starting from eugenol, a natural phenolic compound known to be biologically active. The synthesized compounds were obtained in yields ranging from 54 to 81%. Molecule structures were determined with FT-IR, 1H NMR and 13C NMR spectroscopies. In addition, the inhibitory effects of these substances on acetylcholinesterase (AChE), α-glycosidase (α-Gly), human carbonic anhydrase I (hCA I), and human carbonic anhydrase II (hCA II) enzymes have been investigated. It has been seen that all compounds have a better ability to inhibit compared to existing tried inhibitors. Among these, the best inhibitor against AChE enzyme is 2b (Ki 62.08 ± 11.67 µM and IC50 90.33), and against α-Gly, 2c showed the highest effect (Ki 0.33 ± 0.08 µM and IC50 0.28). The best inhibitor against hCA I, and hCA II enzymes is compound 2f. For hCA I and hCA II, Ki value was measured as 9.68 ± 1.32 and 11.46 ± 2.64 µM and IC50 values as 7.37 and 8.26 µM respectively. The interactions of the studied new propanolamine derivatives with the enzymes were done by molecular docking calculations and their biological activities were compared to the experimental tests. Studied enzymes in molecular docking calculations are acetylcholinesterase (AChE) is PDB ID: 4M0E, α-glycosidase (α-Gly) is PDB ID: 1R47, human carbonic anhydrase isoenzyme I (hCA I) PDB ID: 3LXE is human carbonic anhydrase isoenzyme II (hCA II) is PDB ID: 5 AML.

Novel eugenol bearing oxypropanolamines: Synthesis, characterization, antibacterial, antidiabetic, and anticholinergic potentials.

Five oxypropanol amine derivatives that four of them are novel have been synthesized with high yields and practical methods. in vitro antibacterial susceptibility of Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus strains to synthesized substances were evaluated with agar well-diffusion method by comparison with commercially available drugs. Most of the bacteria were multidrug resistant. It was concluded that these compounds are much more effective than reference drugs. These eugenol bearing oxypropanolamine derivatives were also effective inhibitors against α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) enzymes with Ki values in the range of 0.80 ±â€¯0.24-3.52 ±â€¯1.01 µM for hCA I, 1.08 ±â€¯0.15-3.64 ±â€¯0.92 µM for hCA II, 5.18 ±â€¯0.84-12.46 ±â€¯2.08 µM for α-glycosidase, and 11.33 ±â€¯2.83-32.81 ±â€¯9.73 µM for AChE, respectively.

Novel thymol bearing oxypropanolamine derivatives as potent some metabolic enzyme inhibitors - Their antidiabetic, anticholinergic and antibacterial potentials.

A series of classical and newly synthesized thymol bearing oxypropanolamine compounds were synthesized and characterized. Their in vitro antibacterial activity on A. baumannii, P. aeruginosa, E. coli and S. aureus strains were investigated with agar well diffusion method. The results were compared with commercially available drug active compounds. As well as 3a, 3b and 3c have the most significant antibacterial effect among all the tested compounds; approximately all of them have more antibacterial activity than the reference drugs. These novel thymol bearing oxypropanolamine derivatives were effective inhibitors of the α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase enzymes (AChE) with Ki values in the range of 463.85-851.05 µM for α-glycosidase, 1.11-17.34 µM for hCA I, 2.97-17.83 µM for hCA II, and 13.58-31.45 µM for AChE, respectively.

Architecture of collapse: regime shift and recovery in an hierarchically structured marine ecosystem.

By the late 20th century, a series of events or 'natural experiments', for example the depletion of apex predators, extreme eutrophication and blooms of invasive species, had suggested that the Black Sea could be considered as a large ecosystem 'laboratory'. The events resulted in regime shifts cascading through all trophic levels, disturbing ecosystem functioning and damaging the water environment. Causal pathways by which the external (hydroclimate, overfishing) and internal (food web interactions) drivers provoke regime shifts are investigated. Statistical data analyses supported by an interpretative framework based on hierarchical ecosystem theory revealed mechanisms of hierarchical incorporation of environmental factors into the ecosystem. Evidence links Atlantic teleconnections to Black Sea hydroclimate, which together with fishing shapes variability in fish stocks. The hydroclimatic signal is conveyed through the food web via changes in productivity at all levels, to planktivorous fish. Fluctuating fish abundance is believed to induce a lagged change in competitor jelly plankton that cascades down to phytoplankton and influences water quality. Deprived of the stabilising role of apex predators, the Black Sea's hierarchical ecosystem organisation is susceptible to both environmental and anthropogenic stresses, and increased fishing makes fish stock collapses highly probable. When declining stocks are confronted with burgeoning fishing effort associated with the inability of fishery managers and decision-makers to adapt rapidly to changes in fish abundance, there is overfishing and stock collapse. Management procedures are ineffective at handling complex phenomena such as ecosystem regime shifts because of the shortage of suitable explanatory models. The proposed concepts and models reported here relate the hydroclimate, overfishing and invasive species to shifts in ecosystem functioning and water quality, unravelling issues such as the causality of ecosystem interactions and mechanisms and offering potential for finding ways to reverse regime shifts. We advocate a management approach aiming at restoring ecosystem hierarchy that might mitigate the costly consequences of regime shifts.

Discovery of Potent Carbonic Anhydrase and Acetylcholinesterase Inhibitors: 2-Aminoindan ß-Lactam Derivatives.

ß-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. ß-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that ß-lactams are inhibitors of hCA I, II and AChE. The Ki values of ß-lactams (2a-k) were 0.44-6.29 nM against hCA I, 0.93-8.34 nM against hCA II, and 0.25-1.13 nM against AChE. Our findings indicate that ß-lactams (2a-k) inhibit both carbonic anhydrases (CA) isoenzymes and AChE at low nanomolar concentrations.

Effect of vegetation change from native broadleaf forest to coniferous plantation on selected soil properties.

The objective of this study was to examine the effects of vegetation change from a native broadleaf forest to a coniferous plantation on selected soil properties, including soil texture, pH, organic matter, total nitrogen (N), total phosphorus (P), exchangeable cations (Ca(2+), K(+), Na(+)), and cation exchange capacity (CEC). Results showed that the amount of clay particles, Ca(2+), and K(+) values significantly increased, whereas Na(+), total N, and organic matter and soil pH values decreased on the treatment plot after vegetation change. Soil acidity also increased and soil textural group changed from moderately fine-textured soils (clay loam) to medium-textured soils (loam) under both control and treatment plots. Organic matter, total N, and Na(+) values increased, whereas Ca(2+) concentration decreased through time on the control plot. Soil pH, total P, K(+), and CEC did not show significant changes through time on the control plot.

Investigation of in vitro efficacy of quercetin-meropenem combination in carbapenemase-producing Klebsiella pneumoniae isolates.

INTRODUCTION: In recent years, the rapid spread of carbapenem-resistant K. pneumoniae, their higher mortality rates, and limited treatment alternatives cause difficulties in the treatment of these infections. New treatment alternatives are needed to cope with resistant strains. In recent years, natural products such as Quercetin have started to be preferred in combination studies due to their antimicrobial effects and low side-effect profiles. The aim of this study was to investigate the in vitro efficacy of the combination of Quercetin and Meropenem on carbapenemase-producing (blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP), carbapenem-resistant K.pneumoniae isolates using the checkerboard method. METHODOLOGY: Thirty Carbapenem-resistant K.pneumoniae strains in the culture collection of our laboratory were included in our study. Carbapenemase genes were determined using the Xpert® Carba-R (Cepheid, USA). Synergism with meropenem was assessed by checkerboard analysis, followed by FIC index, and combination index calculation. RESULTS: Twenty (66.6%) strains had OXA-48, 6 (20%) NDM, 1 (3.3%) KPC, 1 (3.3%) OXA-48+NDM genes, and 2 strains (6.6%) gene could not be detected. In the Quercetin and Meropenem combination study, synergy was found in 24 (80%) of the strains; an additive effect was found in 5 (16.6%) and an antagonist effect in 1 (3.3%). In 19 (63.3%) of the strains, meropenem MIC values were below the sensitive limit (MIC ≤ 2 µg/mL). CONCLUSIONS: Although the combination of quercetin and meropenem has a high synergistic effect in carbapenem-resistant K. pneumoniae isolates, it seems that the carbapenemase species affects this situation. however, more work is needed on this subject.

In vitro inhibition of polyphenol oxidase by some new diarylureas.

A new series of N,N'-diarylureas (1-9) was synthesized. These compounds were investigated as inhibitors of polyphenol oxidase (PPO) which had been purified from banana by an affinity gel comprised of Sepharose 4B-l-tyrosine-p-amino benzoic acid. K(i) values for (1), (2), (3), (5), (6), (7) and (8) were determined as 0.285, 17.97, 0.187, 0.108, 0.063, 0.044 and 0.047 mM, respectively. Thus (2) was by far the most effective inhibitor. Interestingly, (4) and (9) behaved as an activator of PPO in this study.

In vitro effect of novel ß-lactam compounds on xanthine oxidase enzyme activity.

Carbazole substituted imines (2a-l) were prepared from N-methyl-3-amino carbazole with different aldehydes. The imines compounds undergo (2+2) cycloaddition reactions with in situ ketenes to produce ß-lactam compounds (3a-l). The ß-lactam compounds were tested as inhibitors of the xanthine oxidase (XO) purified from bovine milk. The results show that these compounds exhibit inhibitory effects on XO at low concentrations with IC(50) values ranging from 21.65 to 58.04 µM. The most effective compound for XO was 4-(4-chlorophenyl)-1-(9-ethyl-9H-carbazol-3-yl)-3-phenylazetidin-2-one with IC(50) of 21.65 µM. The lactams investigated here showed effective XO inhibitory effects, in the same range as the clinically used allopurinol.

Synthesis, characterization, evaluation of metabolic enzyme inhibitors and in silico studies of thymol based 2-amino thiol and sulfonic acid compounds.

Eight new aminothiols (4a-g and 5) and three new sulfonic acid derivatives (6a-c) were synthesized, and their structures were characterized. Inhibitory effects of the obtained compounds on carbonic anhydrase I and II isoforms (hCA I and hCA II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE), enzymes were investigated. The newly synthesized compounds have inhibited hCA I with Kis ranging from 7.11 ± 1.46 nM (6a) to 670.52 ± 300.41 nM (4b) and, hCA II with Kis ranging from 16.83 ± 5.72 nM (6a) to 453.34 ± 208.56 nM (4c). Acetazolamide was employed as the positive control for both hCA isoforms (Ki for hCA I 198.81 ± 14.13 nM and Ki for hCA II 211.42 ± 13.10 nM), and among the new compounds obtained, it was observed that there were compounds that were active at much lower nM levels. All compounds were also evaluated for inhibition of AChE and BChE. They inhibited AChE and BChE enzymes in the range of Ki 5.24 ± 2.27 (6c) - 48.44 ± 21.82 (4g) for AChE and 4.86 ± 0.64 (6c) - 51.75 ± 12.56 (4a) for BChE, and the results were compared with the standard inhibitor Tacrine (Ki: 14.20 ± 8.83 nM toward AChE and Ki: 3.39 ± 1.91 nM for BChE). Cholinesterase (BChE and AChE) inhibitory abilities of all synthesized molecules were also performed in situ and molecular docking and molecular dynamics (MD) simulation studies. The molecular coupling scores of the compounds and the free binding energies calculated by MM/GBSA were found to be compatible. Examining the results obtained from this study shows that it may have the potential to develop new drugs to treat some global patients such as glaucoma and Alzheimer's disease (AD).

Global dataset of species-specific inland recreational fisheries harvest for consumption.

Inland recreational fisheries, found in lakes, rivers, and other landlocked waters, are important to livelihoods, nutrition, leisure, and other societal ecosystem services worldwide. Although recreationally-caught fish are frequently harvested and consumed by fishers, their contribution to food and nutrition has not been adequately quantified due to lack of data, poor monitoring, and under-reporting, especially in developing countries. Beyond limited global harvest estimates, few have explored species-specific harvest patterns, although this variability has implications for fisheries management and food security. Given the continued growth of the recreational fishery sector, understanding inland recreational fish harvest and consumption rates represents a critical knowledge gap. Based on a comprehensive literature search and expert knowledge review, we quantified multiple aspects of global inland recreational fisheries for 81 countries spanning ~192 species. For each country, we assembled recreational fishing participation rate and estimated species-specific harvest and consumption rate. This dataset provides a foundation for future assessments, including understanding nutritional and economic contributions of inland recreational fisheries.

Tetra-substituted phthalocyanines bearing thiazolidine derivatives: synthesis, anticancer activity on different cancer cell lines, and molecular docking studies.

In the first step, (4R)-2-(2-hydroxyphenyl)thiazolidine-4-carboxylic acid (c) and 2-(2-(3,4-dicyanophenoxy)phenyl)thiazolidine-4-carboxylic acid (1) were prepared. Then, the peripherally tetra-substituted metallophthalocyanines [ZnPc (2), CuPc (3), and CoPc (4)] were synthesized by using 1. The structures of the obtained compounds were characterized by common spectroscopic methods. Aggregation behaviors of the tetra-substituted metallophthalocyanines (2-4) were investigated by UV-Vis and fluorescence spectroscopy in the presence/absence of soft metal ions. The electronic spectra of the newly synthesized metallophthalocyanines [ZnPc (2), CuPc (3), and CoPc (4)] were analyzed by the Bayliss method. The fluorescence quantum yield of diamagnetic ZnPc (2) was obtained in DMSO at room temperature. Also, the anticancer activity of the newly synthesized metallophthalocyanine derivatives was studied on C6, DU-145, and WI-38 cell lines and investigated using six concentrations (3.125; 6.25; 12.5; 50; 75; 100 µg L-1). The cell cycle and apoptosis analyses of CuPc (3) were performed. In addition, the chemical and biological activities of 2-(2-(3,4-dicyanophenoxy)phenyl)thiazolidine-4-carboxylic acid (1) and its novel type metallophthalocyanines [ZnPc (2), CuPc (3), and CoPc (4)] were compared with many parameters obtained from the Gaussian software and molecular docking methods.

Charge transfer complex studies between some non-steroidal anti-inflammatory drugs and pi-electron acceptors.

Charge transfer (CT) complexes of some non-steroidal anti-inflammatory drugs, naproxen and etodolac which are electron donors with some pi-acceptors, such as tetracyanoethylene (TCNE), 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), p-chloranil (p-CHL), have been investigated spectrophotometrically in chloroform at 21 degrees C. The coloured products are measured spectrophotometrically at different wavelength depending on the electronic transition between donors and acceptors. Beer's law is obeyed and colours were produced in non-aqueous media. All complexes were stable at least 2 h except for etodolac with DDQ stable for 5 min. The equilibrium constants of the CT complexes were determined by the Benesi-Hildebrand equation. The thermodynamic parameters DeltaH, DeltaS, DeltaG degrees were calculated by Van't Hoff equation. Stochiometries of the complexes formed between donors and acceptors were defined by the Job's method of the continuous variation and found in 1:1 complexation with donor and acceptor at the maximum absorption bands in all cases.

New records of five sponge species (Porifera) for the Black Sea.

The present study deals with five sponge species [Chalinula renieroides, Haliclona (Halichoclona) fulva, H. (Rhizoniera) rosea, Hymedesmia (Hymedesmia) pansa and Ircinia variabilis] belonging to 3 families (Chalinidae, Hymedesmiidae, and Irciniidae) found at one locality (near the opening of Kizilirmak River) on the Black Sea coast of Turkey. All these species are new records for the Black Sea. Three species (Chalinula renieroides, H. (R.) rosea and H. (H.) pansa] are also new records for the marine fauna of Turkey. All these species were previously reported from Mediterranean Sea and the eastern Atlantic Ocean. The morphological and distributional features of these species are presented.

The comparison of automated urine analyzers with manual microscopic examination for urinalysis automated urine analyzers and manual urinalysis.

OBJECTIVES: Urinalysis is one of the most commonly performed tests in the clinical laboratory. However, manual microscopic sediment examination is labor-intensive, time-consuming, and lacks standardization in high-volume laboratories. In this study, the concordance of analyses between manual microscopic examination and two different automatic urine sediment analyzers has been evaluated. DESIGN AND METHODS: 209 urine samples were analyzed by the Iris iQ200 ELITE (Iris Diagnostics, USA), Dirui FUS-200 (DIRUI Industrial Co., China) automatic urine sediment analyzers and by manual microscopic examination. The degree of concordance (Kappa coefficient) and the rates within the same grading were evaluated. RESULTS: For erythrocytes, leukocytes, epithelial cells, bacteria, crystals and yeasts, the degree of concordance between the two instruments was better than the degree of concordance between the manual microscopic method and the individual devices. There was no concordance between all methods for casts. CONCLUSION: The results from the automated analyzers for erythrocytes, leukocytes and epithelial cells were similar to the result of microscopic examination. However, in order to avoid any error or uncertainty, some images (particularly: dysmorphic cells, bacteria, yeasts, casts and crystals) have to be analyzed by manual microscopic examination by trained staff. Therefore, the software programs which are used in automatic urine sediment analysers need further development to recognize urinary shaped elements more accurately. Automated systems are important in terms of time saving and standardization.

Coarctation of the aorta in the adult complicated by poststenotic fusiform aneurysm.

We describe a case of adult coarctation of the aorta, which presented unusually as a poststenotic fusiform aneurysm in a 48-year-old female. She was normotensive and had a history of back pain and palpitations. Under partial cardiopulmonary bypass, the stenosis and the aneurysm were resected and replaced with a Dacron tube graft.