Synthesis and biological activity of 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide derivatives

The synthesis and antimicrobial evaluation of new 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide derivatives was investigated. According to the literature, there are a lot of antimicrobial agents among the pyrimidines and hydrazides, and therefore it seems promising to use 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide as a base object for synthesizing new biologically active substances. 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide was obtained by the hydrazinolysis of ethyl thioacetate, using a 3-fold molar excess of 85 % hydrazine hydrate in ethanol, at room temperature. Interaction of 2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]-acetohydrazide with ketones during boiling in ethanol yielded N-ylidenehydrazides. The solid obtained by concentration was collected, and then purified by recrystallization. The new compounds were characterized by 1H, 13C NMR, IR spectroscopy and elemental analysis. The antibacterial and antifungal activities of the new compounds were analysed using agar diffusion and tenfold broth (pH 7.2 – 7.4) dilution methods, in comparison with the clinical used drugs, ceftriaxone and Pimafucin. The structure–activity studies showed that, depending on the nature of the hydrazide fragment, the newly synthesized compounds exhibited varying degrees of microbial inhibition. Within the same series the antimicrobial activity depends on the nature of the substituent attached to the benzene ring. The investigation of antibacterial screening data revealed that the compounds Nʹ-[1-(4-aminophenyl)ethylidene]-2-[6-methyl-4-(thietan-3-yloxy)pyrimidin-2-ylthio]acetohydrazide, Nʹ-[1-(4-hydroxyphenyl)ethylidene]-2-[6-methyl-4-(thi¬-etan¬-3-yloxy)pyrimidin-2-ylthio]acetohydrazide, Nʹ-[1- (2,5-dihydroxyphenyl) ethylidene]-2-[6-methyl-4-(thietan-3-yloxy)-pyrimidin-2-ylthio]acetohydrazide were found to be more potent than the other synthesized analogues

Green Synthesis of Silver Nanoparticles from Allium cepa L. Peel Extract, Their Antioxidant, Antipathogenic, and Anticholinesterase Activity

The present work deals with the green synthesis and characterization of silver nanoparticles (AgNPs) using Allium cepa (yellowish peel) and the evaluation of its antimicrobial, antioxidant, and anticholinesterase activities. For the synthesis of AgNPs, peel aqueous extract (200 mL) was treated with a 40 mM AgNO3 solution (200 mL) at room temperature, and a color change was observed. In UV-Visible spectroscopy, an absorption peak formation at ~439 nm was the sign that AgNPs were present in the reaction solution. UV-vis, FE-SEM, TEM, EDX, AFM, XRD, TG/DT analyses, and Zetasizer techniques were used to characterize the biosynthesized nanoparticles. The crystal average size and zeta potential of AC-AgNPs with predominantly spherical shapes were measured as 19.47 ± 1.12 nm and −13.1 mV, respectively. Pathogenic microorganisms Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were used for the Minimum Inhibition Concentration (MIC) test. When compared to tested standard antibiotics, AC-AgNPs demonstrated good growth inhibitory activities on P. aeuruginosa, B. subtilis, and S. aureus strains. In vitro, the antioxidant properties of AC-AgNPs were measured using different spectrophotometric techniques. In the β-Carotene linoleic acid lipid peroxidation assay, AC-AgNPs showed the strongest antioxidant activity with an IC50 value of 116.9 µg/mL, followed by metal-chelating capacity and ABTS cation radical scavenging activity with IC50 values of 120.4 µg/mL and 128.5 µg/mL, respectively. The inhibitory effects of produced AgNPs on the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were determined using spectrophotometric techniques. This study provides an eco-friendly, inexpensive, and easy method for the synthesis of AgNPs that can be used for biomedical activities and also has other possible industrial applications

Long non-coding RNAs regulated NF-κB signaling in cancer metastasis: Micromanaging by not so small non-coding RNAs

Cancer metastasis is a major reason for the cancer-associated deaths and a role of long non-coding RNAs (lncRNAs) in cancer metastasis is increasingly being realized. Among the many oncogenic pathways, NF-κB signalling’s involvement in cancer metastasis as a key inflammation-regulatory transcription factor has been a subject of interest for long time. Accumulating data from in vitro as well as in vivo studies along with analysis of clinical cancer tissues points to regulation of NF-κB signalling by lncRNAs with implications toward the onset of cancer metastasis. LncRNAs FOXD2-AS1, KRT19P3 and the NF-κB interacting lncRNA (NKILA) associate with lymph node metastasis and poor prognosis of individual cancers. The role of epithelial-mesenchymal transition (EMT) in cancer metastasis is well known. EMT is regulated by NF-κB and regulation of NF-κB/EMT-induced metastasis by lncRNAs remains a hot topic of research with indications for such roles of lncRNAs MALAT1, SNHG15, CRNDE and AC007271.3. Among the many lncRNAs, NKILA stands out as the most investigated lncRNA for its regulation of NF-κB. This tumor suppressive lncRNA has been reported downregulated in clinical samples representing different human cancers. Mechanistically, NKILA has been consistently shown to inhibit NF-κB activation via inhibition of IκBα phosphorylation and the resulting suppression of EMT. NKILA is also a target of natural anticancer compounds. Given the importance of NF-κB as a master regulatory transcription factor, lncRNAs, as the modulators of NF-κB signaling, can provide alternate targets for metastatic cancers with constitutively active NF-κB.Open Access supported by the Qatar National Library

CircRNAs in Alzheimer's disease: What are the prospects?

Circular RNAs (circRNAs) is a fascinating covalently closed circular non-coding RNA that is abundantly present in the transcriptome of eukaryotic cells. Its versatile nature allows it to participate in a multitude of pathological and physiological processes within the organism. One of its crucial functions is acting as a microRNA sponge, modulating protein transcription levels, and forming interactions with essential RNA-binding proteins. Remarkably, circRNAs demonstrates a specific enrichment in various vital areas of the brain, including the cortex, hippocampus, white matter, and photoreceptor neurons, particularly in aging organisms. This intriguing characteristic has led scientists to explore its potential as a significant biological marker of neurodegeneration, offering promising insights into neurodegenerative diseases like Alzheimer's disease (AD). In AD, there has been an interesting observation of elevated levels of circRNAs in both peripheral blood and synaptic terminals of affected individuals. This intriguing finding raises the possibility that circRNAs may have a central role in the initiation and progression of AD. Notably, different categories of circRNAs, including HDAC9, HOMER1, Cwc27, Tulp4, and PTK2, have been implicated in driving the pathological changes associated with AD through diverse mechanisms. For instance, these circRNAs have been demonstrated to contribute to the accumulation of beta-amyloid, which is a hallmark characteristic of AD. Additionally, these circRNAs contribute to the excessive phosphorylation of tau protein, a phenomenon associated with neurofibrillary tangles, further exacerbating the disease. Moreover, they are involved in aggravating neuroinflammation, which is known to play a critical role in AD's pathogenesis. Lastly, these circRNAs can cause mitochondrial dysfunction, disrupting cellular energy production and leading to cognitive impairment. As researchers delve deeper into the intricate workings of circRNAs, they hope to unlock its full potential as a diagnostic tool and therapeutic target for neurodegenerative disorders, paving the way for innovative treatments and better management of such devastating conditions

Long non-coding RNAs as promising biomarkers and therapeutic targets in cervical cancer

Cervical cancer is the second most common cancer in women. The detection of oncopathologies in the early stages of development is a paramount task of modern medicine, which can be solved only by improving modern diagnostic methods. The use of screening for certain tumor markers could complement modern tests such as testing for oncogenic types of human papillomavirus (HPV), cytology, colposcopy with acetic acid and iodine solutions. Such highly informative biomarkers can be long noncoding RNAs (lncRNAs) that are highly specific compared to the mRNA profile and are involved in the regulation of gene expression. LncRNAs are a class of non-coding RNAs molecules that are typically over 200 nucleotides in length. LncRNAs may be involved in the regulation of all major cellular processes, including proliferation and differentiation, metabolism, signaling pathways, and apoptosis. LncRNAs molecules are highly stable due to their small size, which is also their undoubted advantage. The study of individual lncRNAs as regulators of the expression of genes involved in the mechanisms of oncogenesis cervical cancer can be not only of great diagnostic value, but, as a result, of therapeutic significance in cervical cancer patients. This review article will present the characteristics of lncRNAs that allow them to be used as accurate diagnostic and prognostic tools, as well as to consider them as effective therapeutic targets in cervical cancer

The roles of long noncoding RNAs in atrial fibrillation

Atrial fibrillation (AF) is a common cardiac arrhythmia that often occurs in patients with structural heart disease and is a significant cause of morbidity and mortality in clinical settings. AF is typically associated with significant changes of both the structure of the atria and the cardiac conduction system. AF can result in reduced heart function, heart failure, and various other complications. Current drug therapy for AF patients is often ineffective and may have adverse effects. Radiofrequency ablation is more effective than traditional drug therapy, but this invasive procedure carries potential risks and may lead to postoperative recurrence, limiting the clinical benefits to some extent. Therefore, in-depth research into the molecular mechanisms of AF and exploration of new treatment strategies based on research findings are prerequisites for improving the treatment of AF and the associated cardiac conditions. Long noncoding RNAs (lncRNAs) are a new class of noncoding RNA (ncRNAs) with a length exceeding 200 nt, which regulate gene expression at multiple levels. Increasing evidence suggests that lncRNAs participate in many pathological processes of AF initiation, development, and maintenance, such as structural remodeling, electrical remodeling, renin-angiotensin system anomalies, and intracellular calcium deregulation s. LncRNAs that play key roles in structural and electrical remodeling may become molecular markers and targets for AF diagnosis and treatment, respectively, while lncRNAs critical to autonomic nervous system remodeling may bring new insights into the prognosis and recurrence of AF. This review article provides a synopsis on the up-to-date research findings relevant to the roles of lncRNAs in AF