In the present study, the hepatoprotective effect of 5-benzylidine-2-thiohydantoin (5B2T), a unique derivative of the thiohydantoin group, on liver injury induced by diethylnitrosamine (DEN) in male ...rats was investigated. The experimental animals were divided into three groups, each with 14 rats. Rats in group I were considered to be controls and received only 10% Tween 80. Rats in group II were injected with 200 mg/kg DEN intraperitoneally. Rats in group III were injected with a single dose of DEN 200 mg/kg intraperitoneally and received the treatment orally (50 mg/kg, 5B2T) for two durations, 3 and 6 weeks. At the end of the experiment, blood was collected for the analysis of liver function and pro-inflammatory cytokine IL-6 and tumor necrosis factor α (TNF-α) levels. Additionally, liver specimens were used for histopathological examination and immunohistochemistry. The single intraperitoneal injection of 200 mg/kg DEN into rats resulted in significant elevation of serum enzyme levels of AST, ALT and ALP, which are indicators of hepatocellular damage, along with elevation in TNF-α and IL-6 in the DEN group. The results of both LFTs and ELISA in the treatment group showed improvements and a decline in the levels of the markers. Histopathological examination showed fibrosis, necrosis and infiltration of inflammatory cells in the DEN group, with lower intensity in the treatment group. The results of immunohistochemical staining revealed strong positive staining of both HSA and Ki-67 antibodies in the DEN group, with much lower intensity in the treatment group. The results of the docking study indicated that 5B2T has a remarkable interaction with TNF-α (PDB ID: 1TNF) and human IL-6 (PDB ID: 1IL6) with binding site energies of - 7.1 and - 6.1 (kcal/mol), respectively. The correct absorption and binding between the drug and the receptor was evaluated through computerized molecular docking by using the AutoDock program. The conclusion of the results from the current study reflected the interesting hepatoprotective abilities of 5B2T against DEN-induced hepatocellular damage and cancer in experimental rats.
In recent times, the methods used to evaluate gastric ulcer healing worldwide have been based on visual examinations and estimating ulcer dimensions in experimental animals. In this study, the ...protective effect of rhodanine and 2,4-thiazolidinediones scaffolds compared to esomeprazole was investigated in an ethanol model of stomach ulcers in rats. Pretreatment with experimental treatments or esomeprazole prevented the development of ethanol-induced gastric ulcers. The severity of the lesions and injuries was significantly lower than that of vehicle (10% Tween 80) treated rats. Significant and excellent results were obtained with the compound 6 group, with inhibition percentage and ulcer area values of 97.8% and 12.8 ± 1.1 mm
, respectively. Synthesized compounds 2, 7 and 8 exhibited inhibition percentages and ulcer areas of 94.3% and 31.2 ± 1.1 mm
, 91. 3% and 48.1 ± 0. 8 mm
, 89. 5% and 57. 6 ± 1. 2 mm
, and 89. 1% and 60.3 ± 0. 8 mm
, respectively. These biological outcomes are consistent with the docking studies in which Compounds 7 and 8 showed remarkable binding site affinities toward human H+/K+-ATPase α protein (ID: P20648), rat H+/K+-ATPase α protein (ID: P09626), and Na+/K+-ATPase crystal structure (PDB ID:2ZXE) with binding site energies of - 10.7, - 9.0, and - 10.4 (kcal/mol) and - 8.7, - 8.5, and - 8.0 (kcal/mol), respectively. These results indicate that these test samples were as effective as esomeprazole. Likewise, immunohistochemical staining of antiapoptotic (BCL2) and tumor suppressor (P53) proteins showed strong positive marks in the10% Tween 80- treated group, opposing the mild staining results for the esomeprazole-treated group. Similarly, the staining intensity of the group treated with Compounds 2-8 was variable for both proteins.
Combination therapies have been studied by many researchers using different techniques and methods to solve some solid drug problems and improve more effective treatments for humans and animals. One ...of the more significant findings to emerge from this study is that the combination of pharmaceutical agents by using pharmaceutical deep eutectic solvents (PDESs) in order to produce dual action drugs and reduce the drug resistance. The major objective of this study was to investigate the dual functionality of drugs (antioxidant and antibacterial activity) via the principle of PDESs. The produced PDESs were characterized via different techniques, namely differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and UV-Vis spectrophotometry. We herein tested a panel of novel liquid formulations of didecyldimethylammonium bromide (DDMAB) against a selection of pathogenic bacteria, classifying their spectrum of activity against Gram-positive and Gram-negative bacteria. The current study found that the PDESs can be used to produce drugs with dual functionalities. The produced PDES from (ascorbic acid: DDMAB) exhibits stronger antibacterial activity against Gram-positive
Staphyloccocus aureus
and
Staphyloccocus epidermidis
than gram negatives. One of the most interesting PDESs studied in this research was that of DDMAB and ascorbic acid. This forms a eutectic which is far from the solid drugs issues and shows dual functionality like antibacterial and antioxidant activity. This study has found that there is a correlation between the molecular docking study and the biological activities of the combined drugs.
Graphical Abstract
Racemization has a large impact upon the biological properties of molecules but the chemical scope of compounds with known rate constants for racemization in aqueous conditions was hitherto limited. ...To address this remarkable blind spot, we have measured the kinetics for racemization of 28 compounds using circular dichroism and 1H NMR spectroscopy. We show that rate constants for racemization (measured by ourselves and others) correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations. Such calculations thus provide predictions of the second‐order rate constants for general‐base‐catalyzed racemization that are usefully accurate. When applied to recent publications describing the stereoselective synthesis of compounds of purported biological value, the calculations reveal that racemization would be sufficiently fast to render these expensive syntheses pointless.
The racemization potential of complex organic molecules has been predicted using simple quantum mechanical calculations and a group additivity scheme. Organic chemists can first check whether a given synthetic target will be configurationally stable before embarking on a potentially lengthy and expensive chiral synthesis.
Racemization has long been an ignored risk in drug development, probably because of a lack of convenient access to good tools for its detection and an absence of methods to predict racemization risk. ...As a result, the potential effects of racemization have been systematically underestimated. Areas covered: Herein, the potential effects of racemization are discussed through a review of drugs for which activity and side effects for both enantiomers are known. Subsequently, drugs known to racemize are discussed and the authors review methods to predict racemization risk. Application of a method quantitatively predicting racemization risk to databases of compounds from the medicinal chemistry literature shows that success in clinical trials is negatively correlated with racemization risk. Expert opinion: It is envisioned that a quantitative method of predicting racemization risk will remove a blind spot from the drug development pipeline. Removal of the blind spot will make drug development more efficient and result in less late-stage attrition of the drug pipeline.
Introduction
During the previous year, a variety of serious neurological problems associated with the COVID-19 vaccination have been documented, including encephalopathy, Guillain-Barré syndrome, ...transverse myelitis, and Bell’s palsy.
Objective
In the current study, neurological complications reported post-COVID-19 vaccination were systematically reviewed. The current meta-analysis aims to provide clinicians with a comprehensive understanding of this uncommon adverse event.
Method
Web of Science, MEDLINE on OVID, PubMed, and Google Scholar were searched for English-language papers published after January 1, 2020.
Result
Thirty articles were included in this study (21 case series and 9 cohort studies). The studies comprised 22,780 patients who got COVID-19 vaccinations and had at least 1 neurological adverse event. Across the majority of event types, females (54%) reported more adverse events than males (40%). The median duration from vaccination to the development of neurological symptoms was 12 days (0-41 days) in case series studies and 10 days (0-30 days) in cohort studies. Stroke is by far the most common neurological side effect of SARS-CoV-2 vaccines, followed by Bell’s palsy and seizures.
Conclusion
Concerns regarding the safety of COVID-19 vaccinations are being backed up by a growing number of studies that demonstrate neurological side effects.
Coronavirus disease 2019 (COVID-19) pandemic, is a newly conducted respiratory disease caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). The current study aims ...to estimate the neurological diseases which develop after COVID-19 infection.
This is a single center retrospective case series conducted in seven months. the patients were collected in an out-patient clinic. Diagnosis of COVID-19 and the way of diagnosis is confirmed through either polymerase chain reaction (PCR) test for COVID-19 and/or typical findings on chest computed tomography scan (CT scan). Patients developed neurological symptoms after being infected with COVID-19. Symptoms have to be developed within less than 6 months of recovery, or developed during illness and persisted after recovery.
A total number of 59 patients infected with SARS-CoV2 were included. The majority of the patients had mild symptoms 32 (54%), 12 (20%) patients developed severe symptoms. Headache was the most common presenting symptom 27(46%) followed by fatigue in 8 (13.5%). The majority of the patients 55 (91.6%) presented with no focal signs. MRI was done for 27 (46%) patients without abnormal finding in 22 cases. Nearly 22 (37.3%) cases were diagnosed as recurrent episodes of migraine or new onset of migraine. All patients were managed according to the underlying pathology, only (28, 47.5%) patients were known to be completely recovered.
SARS-CoV2 can invade and cause inflammation in the central and peripheral nervous systems. It is responsible for many neurological problems. More studies are necessary to analyze the long term effect of the virus on the nervous system.
•COVID-19 survivors might be at risk of developing neurological disorders.•The exact prevalence and risk groups are yet to be established.•This study aims to estimate the post-COVID-19 neurological sequelae.
The hepatoprotective effect of synthesized 3-(3,5-bis (trifluoromethyl) phenyl)-5-methyl-1-((1-methyl-1H-pyrrol-2-yl) methyl)-2-thioxoimidazolidin-4-one (3FL-M) was evaluated against diethyl ...nitrosamine-induced liver injury (DEN). Wistar rats were divided into 3 groups as: placebo (received 10% tween 80%), hepatotoxic control (injected with 200 mg/kg of DEN) and treatment (injected 200 mg/kg of DEN and received 50 mg/kg oral feeding of the synthesized 3FL-M). Half the number of the rats were sacrificed on 2nd week of the experiment, whereas the other half were sacrificed after 6 weeks. Blood was collected to run liver biochemical analysis, and to evaluate pro-inflammatory cytokines tumor necrosis factor-alpha TNF-alpha and interleukine6 IL-6. Liver sections were used to detect nuclear protein ki-67 and hepatocyte specific antibody HSA. 3FL-M was subjected to molecular docking calculations based on binding affinities towards TNF-alpha and IL-6. DEN-treated rats showed elevation in the liver serum enzymes as well as pro-inflammatory cytokines with clear destruction of the hepatic architecture, in contrast 3FL-M treated rats showed normalized liver enzymes and cytokines levels with resolution of the hepatocytes. Molecular modelling revealed that 3FL-M exhibited the significant affinities toward the binding pocket of the TNF-alpha and IL-6, however, further studies is recommended for developing it as a chemotherapeutic drug-like molecule. KEY WORDS: DEN, Hepatoprotective, TNF-alpha, IL-6, Molecular docking
Racemization has a large impact upon the biological properties of molecules but the chemical scope of compounds with known rate constants for racemization in aqueous conditions was hitherto limited. ...To address this remarkable blind spot, we have measured the kinetics for racemization of 28 compounds using circular dichroism and 1H NMR spectroscopy. We show that rate constants for racemization (measured by ourselves and others) correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations. Such calculations thus provide predictions of the second‐order rate constants for general‐base‐catalyzed racemization that are usefully accurate. When applied to recent publications describing the stereoselective synthesis of compounds of purported biological value, the calculations reveal that racemization would be sufficiently fast to render these expensive syntheses pointless.
Das Racemisierungspotential komplexer organischer Moleküle wurde mithilfe einfacher quantenmechanischer Rechnungen und einem Gruppenadditivitätsschema vorhergesagt. Organochemiker können damit erst überprüfen, ob vorgegebene Syntheseziele strukturell stabil sind, bevor sie eine potentiell langwierige und kostenintensive chirale Synthese beginnen.
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