Synthesis, and bio-evaluation studies of new isothiocyanate derivatives with respect to COX inhibition and HS release profiles.

The development of HS-donating derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) is considered important to reduce or overcome their gastrointestinal side effects. Sulforaphane, one of the most extensively studied isothiocyanates (ITCs), effectively releases HS at a slow rate. Thus, we rationally designed, synthesized, and characterized new ITC derivatives (I1-3 and I1a-e) inspired by the natural compound sulforaphane.

Novel benzothiazole/benzothiazole thiazolidine-2,4-dione derivatives as potential FOXM1 inhibitors: In silico, synthesis, and in vitro studies.

The oncogenic transcription factor FOXM1 overexpressed in breast and other solid cancers, is a key driver of tumor growth and progression through complex interactions, making it an attractive molecular target for the development of targeted therapies. Despite the availability of small-molecule inhibitors, their limited specificity, potency, and efficacy hinder clinical translation. To identify effective FOXM1 inhibitors, we synthesized novel benzothiazole derivatives (KC10-KC13) and benzothiazole hybrids with thiazolidine-2,4-dione (KC21-KC36).

A drug repurposing study identifies novel FOXM1 inhibitors with in vitro activity against breast cancer cells.

FOXM1, a proto-oncogenic transcription factor, plays a critical role in cancer development and treatment resistance in cancers, particularly in breast cancer. Thus, this study aimed to identify potential FOXM1 inhibitors through computational screening of drug databases, followed by in vitro validation of their inhibitory activity against breast cancer cells. In silico studies involved pharmacophore modeling using the FOXM1 inhibitor, FDI-6, followed by virtual screening of DrugBank and Selleckchem databases.

Semantic Harmonization of Alzheimer's Disease Datasets Using AD-Mapper.

Background: Despite numerous past endeavors for the semantic harmonization of Alzheimer's disease (AD) cohort studies, an automatic tool has yet to be developed.

Objective: As cohort studies form the basis of data-driven analysis, harmonizing them is crucial for cross-cohort analysis. We aimed to accelerate this task by constructing an automatic harmonization tool.

Synthesis of new imine-/amine-bearing imidazo[1,2-a]pyrimidine derivatives and screening of their cytotoxic activity.

Imidazo[1,2-]pyrimidine derivatives bearing imine groups (-) were successfully synthesized in moderate to good yields using microwave-assisted heating. Corresponding amine derivatives (-) were also obtained by the reduction reaction of the imine derivatives (-). All synthesized products were characterized by FT-IR, H NMR, C NMR, and LC-MS spectroscopic techniques.

Novel etodolac derivatives as eukaryotic elongation factor 2 kinase (eEF2K) inhibitors for targeted cancer therapy.

Eukaryotic elongation factor 2 kinase (eEF2K) has been shown to be an important molecular driver of tumorigenesis and validated as a potential novel molecular target in various solid cancers including triple negative breast cancer (TNBC). Therefore, there has been significant interest in identifying novel inhibitors of eEF2K for the development of targeted therapeutics and clinical translation. Herein, we investigated the effects of indole ring containing derivatives of etodolac, a nonsteroidal anti-inflammatory (NSAID) drug, as potential eEF2K inhibitors and we designed and synthesized seven novel compounds with a pyrano[3,4-] indole core structure.

Effectiveness of the polyglycolic acid patch in preventing prolonged air leakage after pulmonary decortication.

Aim: This study aimed to investigate the effectiveness of an absorbable polyglycolic acid patch (PGA) in the early prevention of alveolar air leaks after pulmonary decortication operations.

Methods: Between January 2016 and December 2019, files of 185 patients with pleural effusion, empyema, or hemothorax were examined retrospectively. Thirty-five patients who underwent decortication surgery were included in the study.

Identifying highly effective coumarin-based novel cholinesterase inhibitors by in silico and in vitro studies.

Inhibition of high cholinesterase levels including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), is one of the most important strategies for the treatment of Alzheimer's disease (AD). Clinically limited drugs are used in the treatment of AD, so there is a need to find new effective inhibitors today. Therefore, in this study, synthesized six coumarin carboxamides (A1, A2, B1-B4) were evaluated against AChE and BChE by combined in silico and in vitro studies.

The effect of the shock index and scoring systems for predicting mortality among geriatric patients with upper gastrointestinal bleeding: a prospective cohort study.

Background: Gastrointestinal (GI) bleeding is an important cause of mortality and morbidity among geriatric patients.

Objective: To investigate whether the shock index and other scoring systems are effective predictors of mortality and prognosis among geriatric patients presenting to the emergency department with complaints of upper GI bleeding.

Design And Setting: Prospective cohort study in an emergency department in Bursa, Turkey.

A prospective study of wake-up stroke patients presenting to the emergency department: a single-center cohort study.

Introduction: This study aims to prospectively examine patients with ischemic wake-up stroke (WUS) presenting to the emergency department, to investigate the risk factors affecting the mortality occurring within 28, 90, and 180 days, and to create a new scoring system for the prediction of 28-day mortality.

Materials And Method: Patients who presented to the emergency department with WUS findings between 01.07.

Investigation of highly cited publications related to vaccines against COVID-19: current state and future predictions.

Background: Since the date of declaring the COVID-19 outbreak a pandemic by the World Health Organization (March 11, 2020), vaccine studies have been initiated. In this article, we aimed to investigate highly cited articles on vaccines and guide researchers for future studies.

Material And Methods: Publications with 6 or more citations (highly cited publications) were extracted from Web of Science (WoS) database.

Spontaneous pneumomediastinum incidence and clinical features in non-intubated patients with COVID-19.

Objectives: To evaluate the presentation characteristics and disease course of seven patients with COVID-19 who spontaneously developed pneumomediastinum without a history of mechanical ventilation.

Methods: A total of seven non-intubated patients with COVID-19, of age ranging from 18-67 years, who developed spontaneous pneumomediastinum between 01 April and 01 October 2020 were included in the study. Patients' demographic data, clinical variables, and laboratory values were examined.

Novel inhibitors of eukaryotic elongation factor 2 kinase: In silico, synthesis and in vitro studies.

Eukaryotic elongation factor 2 kinase (eEF2K) is an unusual alpha kinase whose expression is highly upregulated in various cancers and contributes to tumor growth, metastasis, and progression. More importantly, eEF2K expression is associated with poor clinical outcome and shorter patient survival in breast, lung and ovarian cancers. Therefore, eEF2K is an emerging molecular target for development of novel targeted therapeutics and precision medicine in solid cancers.

Correction to "Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel EF2 Kinase Inhibitor Suppresses Breast Cancer Growth ".

[This corrects the article DOI: 10.1021/acsptsci.1c00030.

New nimesulide derivatives with amide/sulfonamide moieties: Selective COX-2 inhibition and antitumor effects.

Seventeen new amide/sulfonamide containing nimesulide derivatives were synthesized and characterized by several spectroscopic techniques and primarily investigated for their inhibitory potential on COX enzymes and other pro-inflammatory factors. Experimental analyses showed that among seventeen compounds, N8 and N10 have remarkable potency and selectivity for the COX-2 enzyme over COX-1 at very low doses as compared to nimesulide. Moreover, both N8 and N10 selectively reduced the Lipopolysaccharide (LPS)-stimulated COX-2 mRNA expression level while the COX-1 level remained stable.

Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel EF2 Kinase Inhibitor Suppresses Breast Cancer Growth .

Eukaryotic elongation factor 2 kinase (eEF-2K) is an unusual alpha kinase involved in protein synthesis through phosphorylation of elongation factor 2 (EF2). eEF-2K is highly overexpressed in breast cancer, and its activity is associated with significantly shortened patient survival and proven to be a potential molecular target in breast cancer. The crystal structure of eEF-2K remains unknown, and there is no potent, safe, and effective inhibitor available for clinical applications.

Prodrugs for nitroreductase based cancer therapy-4: Towards prostate cancer targeting: Synthesis of N-heterocyclic nitro prodrugs, Ssap-NtrB enzymatic activation and anticancer evaluation.

In this study, various N-heterocyclic nitro prodrugs (NHN1-16) containing pyrimidine, triazine and piperazine rings were designed and synthesized. The final compounds were identified using FT-IR, H NMR, C NMR as well as elemental analyses. Enzymatic activities of compounds were conducted by using HPLC analysis to investigate the interaction of substrates with Ssap-NtrB nitroreductase enzyme.

Delivery of Small Molecule EF2 Kinase Inhibitor for Breast and Pancreatic Cancer Cells Using Hyaluronic Acid Based Nanogels.

Purpose: To evalauted natural polymeric biomaterials including hyaluronic acid (HA) and its copolymeric form HA:Suc nanoparticles (NPs) as drug carrier systems for delivery of hydrophobic small molecule kinase EF2-kinase inhibitor in breast and pancreatic cancer cells.

Methods: In vitro cellular uptake studies of Rhodamine 6G labaled HA:Suc nanoparticles were evaluated by using flow cytometry analysis and fluorescent microscopy in breast (MDA-MB-231 and MDA-MB-436) and pancreatic cancer cells (PANC-1 and MiaPaca-2). Besides, in vitro release study of compound A (an EF2-kinase inhibitor) as a model hydrophobic drug was performed in the cancer cells.

Design, Synthesis, and Molecular Modeling Studies of Novel Coumarin Carboxamide Derivatives as eEF-2K Inhibitors.

Eukaryotic elongation factor-2 kinase (eEF-2K) is an unusual alpha kinase commonly upregulated in various human cancers, including breast, pancreatic, lung, and brain tumors. We have demonstrated that eEF-2K is relevant to poor prognosis and shorter patient survival in breast and lung cancers and validated it as a molecular target using genetic methods in related tumor models. Although several eEF-2K inhibitors have been published, none of them have shown to be potent and specific enough for translation into clinical trials.

In vitro and in silico studies of nitrobenzamide derivatives as potential anti-neuroinflammatory agents.

Communicated by Ramaswamy H. Sarma.

PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY- 2: Novel amide/Ntr combinations targeting PC3 cancer cells.

The use of nitroreductases (NTR) that catalyze the reduction of nitro compounds by using NAD(P)H in GDEPT (Gene-directed enzyme prodrug therapy) studies which minimize toxicity at healthy cells and increases concentration of drugs at cancer cells is remarkable. Discovery of new prodrug/NTR combinations is necessary to be an alternative to known prodrug candidates such as CB1954, SN23862, PR-104A. For this aim, nitro containing aromatic amides (A1-A23) were designed, synthesized, performed in silico ADMET and molecular docking techniques in this study.

Structure prediction of eukaryotic elongation factor-2 kinase and identification of the binding mechanisms of its inhibitors: homology modeling, molecular docking, and molecular dynamics simulation.

Protein kinases emerged as one of the most successful families of drug targets due to their increased activity and involvement in mediating critical signal transduction pathways in cancer cells. Recent evidence suggests that eukaryotic elongation factor 2 kinase (eEF-2K) is a potential therapeutic target for treating some highly aggressive solid cancers, including lung, pancreatic and triple-negative breast cancers. Thus, several compounds have been developed for the inhibition of the enzyme activity, but they are not sufficiently specific and potent.

Hyaluronic acid and hyaluronic acid: Sucrose nanogels for hydrophobic cancer drug delivery.

Porous and biodegradable hyaluronic acid (HA) nanogel and their copolymeric forms with sucrose (Suc), HA:Sucrose (HA:Suc) nanogels, were synthesized by employing glycerol diglycidyl ether (GDE) as crosslinker with a single step reaction in surfactant-free medium. The size of the nanogels was determined as 150 ± 50 nm in dried state from SEM images and found to increase to about 540 ± 47 nm in DI water measured with DLS measurements. The surface areas of HA and HA:Suc nanogels were measured as 18.