Screening and toxicity evaluation of natural compounds as adenosine 2a and 2b receptor ligands: insights from molecular docking, dynamics, and ADMET analysis.

Recent studies suggest that immunological and inflammatory responses in cardiovascular disorders, such as hypertension, myocardial infarction, ischemia injury, heart failure, arrhythmias, and atherosclerosis, may be affected by changes in the adenosine system. Pharmacological modulation of adenosine occurs through its receptor subtypes. In numerous preclinical studies, the activation of adenosine receptor 2A (AR) or the blockade of adenosine receptor 2B (AR) has shown promising results against cardiovascular diseases.

Organohalogen chalcones: design, synthesis, ADMET prediction, molecular dynamics study and inhibition effect on acetylcholinesterase and carbonic anhydrase.

In an effort to discover potential acetylcholinesterase (AChE) and carbonic anhydrase (CA) inhibitors, a novel series of organohalogen chalcone derivatives (12-20, 23-30) was synthesized, and their chemical structures were characterized by spectral analysis. They showed a highly potent inhibition effect on AChE and hCAs (K values range from 5.07 ± 0.

Delayed versus primary sternal closure for left ventricular assist device implantation: Impact on mechanical circulatory support infections.

Background: Delayed sternal closure may be required after left ventricular assist device (LVAD) implantation due to coagulopathy or hemodynamic instability. There is conflicting data regarding infection risk.

Methods: We performed a single-center, retrospective analysis of patients who received their first LVAD between May 2012 and January 2021.

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 Ks ranging from 7.

Development of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors.

Sixteen compounds () were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound was the most potent inhibitor against MAO-B with an IC value of 0.

Histological assessment of liver and stomach damage caused by pyridazinone derivative antidepressant agents.

Depression is a serious psychological disorder that affects a significant population. We investigated the antidepressant activities of four pyridazinone derivatives that contain the hydrazide moiety using the forced swimming test (FST). The compounds tested exhibited good antidepressant activity compared to duloxetine.

Renewables as a pathway to environmental sustainability targets in the era of trade liberalization: empirical evidence from Turkey and the Caspian countries.

The quest for improved environmental quality through low-carbon emission has been explored in this study in the wake of the growing call for a transition to renewable energy use amidst widening trade relations between Turkey and the countries in the Caspian region including Azerbaijan, Iran, Kazakhstan, Russia, and Turkmenistan. This study draws strength from the United Nations Sustainable Development Goals (UN-SDGs) and their impact by 2030. These SDGs encompass pertinent targets on responsible energy consumption (SDG-12), access to clean and affordable energy (SDG-7), and climate change action (SDG-13).

Synthesis, Cytotoxicity and Anti-Proliferative Activity Against AGS Cells of New 3(2)-Pyridazinone Derivatives Endowed with a Piperazinyl Linker.

Novel twenty-three 3(2)-pyridazinone derivatives were designed and synthesized based on the chemical requirements related to the anti-proliferative effects previously demonstrated within this scaffold. The introduction of a piperazinyl linker between the pyridazinone nucleus and the additional (un)substituted phenyl group led to some compounds endowed with a limited cytotoxicity against human gingival fibroblasts (HGFs) and good anti-proliferative effects against gastric adenocarcinoma cells (AGS) as evaluated by MTT and LDH assays, using doxorubicin as a positive control. Successive analyses revealed that the two most promising representative compounds ( and ) could exert their effects by inducing oxidative stress as demonstrated by the hydrogen peroxide release and the morphological changes (cell blebbing) revealed by light microscopy analysis after the haematoxylin-eosin staining.

Monoamine Oxidase-B (MAO-B) Inhibitors in the Treatment of Alzheimer's and Parkinson's Disease.

Background: The MAO enzyme is presented in the brain and peripheral tissues and is a significant enzyme that is responsible for the deamination of biogenic amines and thus the regulation of neurotransmitter levels. The reaction of these neurotransmitters with the MAO enzyme produces aldehyde and free amine. MAO enzyme consists of two isoforms, MAO-A and MAO-B, which are characterized by amino acid sequence, three-dimensional structure, substrate preference, and inhibitor selectivity.

An efficient synthesis of novel di-heterocyclic benzazole derivatives and evaluation of their antiproliferative activities.

A series of unsymmetrical nine di-heterocyclic compounds of benzazole derivatives were synthesized at one step via cyclization reaction. The compounds evaluated for cytotoxic activity against A549, A498, HeLa, and HepG2 cancer cell lines. The biological evaluation results show that and exhibit better activity against HepG2 and HeLa cancer cell lines.

Head-to-head bisbenzazole derivatives as antiproliferative agents: design, synthesis, in vitro activity, and SAR analysis.

In the present work, a series of bisbenzazole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of these compounds was investigated using MTT assay. Bisbenzazole derivatives showed significant antiproliferative activity against all the four tested cancer cell lines.

Synthesis and biological evaluation of new 3(2)-pyridazinone derivatives as non-toxic anti-proliferative compounds against human colon carcinoma HCT116 cells.

Novel 3(2)-pyridazinone derivatives were designed, synthesised in satisfactory yields and evaluated in different experimental assays to assess their preliminary toxicity and anti-proliferative effects against HCT116 cell lines . lethality test provided LC values >100 µg/mL for all compounds. Successive assays revealed that some compounds were endowed with a promising anti-proliferative effect against HCT116 cells, alone or stimulated by serotonin as a pro-inflammatory factor in order to mimick an inflamed model of cancer cell microenvironment.

Synthesis, molecular modelling and biological activity of some pyridazinone derivatives as selective human monoamine oxidase-B inhibitors.

Background: Since brain neurotransmitter levels are associated with the pathology of various neurodegenerative diseases like Parkinson and Alzheimer, monoamineoxidase (MAO) plays a critical role in balancing these neurotransmitters in the brain. MAO isoforms appear as promising drug targets for the development of central nervous system agents. Pyridazinones have a broad array of biological activities.

The association between cardiac resynchronization therapy response and sexual activity in patients with heart failure.

Background: Sexual activity is an important indicator of quality of life and is significantly impaired in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) has positive effects on cardiac dysfunction and endothelial dysfunction that lead to erectile dysfunction (ED). We aimed to evaluate whether CRT may improve sexual activity in patients with HF.

Nesfatin-1 levels in patients with slow coronary flow.

Background: Nesfatin-1 is a novel anorectic neuropeptide with potent metabolic regulatory effects.

Aim: We aimed to evaluate the relationship between nesfatin-1 levels and slow coronary flow (SCF).

Methods: A total of 60 consecutive patients with SCF and 60 consecutive patients with normal coronary flow (NCF) were enrolled into the study.

Coumarin or benzoxazinone based novel carbonic anhydrase inhibitors: synthesis, molecular docking and anticonvulsant studies.

Among many others, coumarin derivatives are known to show human carbonic anhydrase (hCA) inhibitory activity. Since hCA inhibition is one of the underlying mechanisms that account for the activities of some antiepileptic drugs (AEDs), hCA inhibitors are expected to have anti-seizure properties. There are also several studies reporting compounds with an imidazole and/or benzimidazole moiety which exert these pharmacological properties.