Rational design and synthesis of novel phenyltriazole derivatives targeting MRSA cell wall biosynthesis.

Antimicrobial resistance in methicillin-resistant (MRSA) is a major global health challenge. This study reports the design and synthesis of novel phenyltriazole derivatives as potential anti-MRSA agents. The new scaffold replaces the thiazole core with a 1,2,3-triazole ring, enhancing antimicrobial efficacy and physicochemical properties.

Novel bis-benzimidazole-triazole hybrids: anticancer study, in silico approaches, and mechanistic investigation.

Aim: Benzimidazole-triazole conjugates are very active hotspot for design and synthesis of promising anticancer agents. The target analogs showed potent and selective cytotoxicity over different cancer cell lines for breast and lung ones.

Materials & Methods: A new series of bis-1,4-disubstituted-1,2,3-triazoles moieties conjugated with a 2-mercapto-benzimidazole 4a-h and 7a-g was synthesized via the click cycloaddition (CuAAC) reaction.

Exploration of cytotoxicity of iodoquinazoline derivatives as inhibitors of both VEGFR-2 and EGFR: Molecular docking, ADMET, design, and syntheses.

Novel inhibitors of epidermal growth factor receptor (EGFR)/vascular endothelial growth factor receptor-2 (VEGFR-2) were synthesized based on the iodoquinazoline scaffold linked to different heteroaromatic, aromatic, and/or aliphatic moieties. The novel derivatives were in vitro examined for anticancer activities against A549, HCT116, michigan cancer foundation-7 (MCF-7), and HepG2 cells. Molecular modeling was applied to discover their orientation of binding with both VEGFR-2 and EGFR active sites.

Hepatic stearoyl-CoA desaturase-1 deficiency induces fibrosis and hepatocellular carcinoma-related gene activation under a high carbohydrate low fat diet.

Stearoyl-CoA desaturase-1 (SCD1) is a pivotal enzyme in lipogenesis, which catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated fatty acids, whose ablation downregulates lipid synthesis, preventing steatosis and obesity. Yet deletion of SCD1 promotes hepatic inflammation and endoplasmic reticulum stress, raising the question of whether hepatic SCD1 deficiency promotes further liver damage, including fibrosis. To delineate whether SCD1 deficiency predisposes the liver to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), we employed in vivo SCD1 deficient global and liver-specific mouse models fed a high carbohydrate low-fat diet and in vitro established AML12 mouse cells.

Effect of medication adherence on quality of life, activation measures, and health imagine in the elderly people: a cross-sectional study.

Background: Usually, old age brings a poor quality of life due to illness and frailty. To prolong their lives and ensure their survival, all elderly patients with chronic diseases must adhere to their medications. In our study, we investigate medication adherence for elderly patients and its impact on the general health of the patient.

Anticancer evaluations of iodoquinazoline substituted with allyl and/or benzyl as dual inhibitors of EGFR and EGFR: design, synthesis, ADMET and molecular docking.

Fifteen new iodoquinazoline derivatives, 5a,b to 18, are reported in this study and their anticancer evaluation as dual inhibitors of EGFR and EGFR. The new derivatives were designed according to the target of structural requirements of receptors. Cytotoxicity of our compounds was evaluated against MCF-7, A549, HCT116 and HepG2 cell lines using MTT assay.

N- and s-substituted Pyrazolopyrimidines: A promising new class of potent c-Src kinase inhibitors with prominent antitumor activity.

In this work, readily achievable synthetic pathways were utilized for construction of a library of N/S analogues based on the pyrazolopyrimidine scaffold with terminal alkyl or aryl fragments. Subsequently, we evaluated the anticancer effects of these novel analogs against the proliferation of various cancer cell lines, including breast, colon, and liver lines. The results were striking, most of the tested molecules exhibited strong and selective cytotoxic activity against the MDA-MB-231 cancer cell line; IC 1.

Retraction: Large Pleural Lipoma Manifesting With Chronic Shoulder Pain.

[This retracts the article DOI: 10.7759/cureus.21113.

Iodoquinazoline-derived VEGFR-2 and EGFR dual inhibitors: Design, synthesis, molecular docking and anticancer evaluations.

Herein, we report the synthesis of a series of new fourteen iodoquinazoline derivatives 7a-c to 13a-e and their evaluation as potential anticancer agents via dual targeting of EGFR and VEGFR-2. The new derivatives were designed according to the target receptors structural requirements. The compounds were evaluated for their cytotoxicity against HepG2, MCF-7, HCT116 and A549 cancer cell lines using MTT assay.

Design, synthesis, docking, ADMET and anticancer evaluations of -alkyl substituted iodoquinazoline derivatives as dual VEGFR-2 and EGFR inhibitors.

Fifteen new 1-alkyl-6-iodoquinazoline derivatives 5a-d to 9a-e were designed and synthesized and their anticancer activities were evaluated against HepG2, MCF-7, HCT116 and A549 cancer cell lines dual targeting of EGFR and VEGFR-2. The newly synthesized compounds were designed based on the structure requirements of the target receptors and were confirmed using spectral data. Compound 9c showed the highest anticancer activities with EC = 5.

Development of Novel Class of Phenylpyrazolo[3,4-]pyrimidine-Based Analogs with Potent Anticancer Activity and Multitarget Enzyme Inhibition Supported by Docking Studies.

Phenylpyrazolo[3,4-]pyrimidine is considered a milestone scaffold known to possess various biological activities such as antiparasitic, antifungal, antimicrobial, and antiproliferative activities. In addition, the urgent need for selective and potent novel anticancer agents represents a major route in the drug discovery process. Herein, new aryl analogs were synthesized and evaluated for their anticancer effects on a panel of cancer cell lines: MCF-7, HCT116, and HePG-2.

Using Protein Fingerprinting for Identifying and Discriminating Methicillin Resistant Isolates from Inpatient and Outpatient Clinics.

In hospitals and other clinical settings, Methicillin-resistant (MRSA) is a particularly dangerous pathogen that can cause serious or even fatal infections. Thus, the detection and differentiation of MRSA has become an urgent matter in order to provide appropriate treatment and timely intervention in infection control. To ensure this, laboratories must have access to the most up-to-date testing methods and technology available.

Introducing of novel class of pyrano[2,3-]pyrazole-5-carbonitrile analogs with potent antimicrobial activity, DNA gyrase inhibition, and prominent pharmacokinetic and CNS toxicity profiles supported by molecular dynamic simulation.

Microbiological DNA gyrase is recognized as an exceptional microbial target for the innovative development of low-resistant and more effective antimicrobial drugs. Hence, we introduced a one-pot facile synthesis of a novel pyranopyrazole scaffold bearing different functionalities; substituted aryl ring, nitrile, and hydroxyl groups. All new analogs were characterized with full spectroscopic data.

Modulation of NRF2/KEAP1-Mediated Oxidative Stress for Cancer Treatment by Natural Products Using Pharmacophore-Based Screening, Molecular Docking, and Molecular Dynamics Studies.

Oxidative stress plays a significant role in the development of cancer. Inhibiting the protein-protein interaction (PPI) between Keap1 and Nrf2 offers a promising strategy to activate the Nrf2 antioxidant pathway, which is normally suppressed by the binding of Keap1 to Nrf2. This study aimed to identify natural compounds capable of targeting the kelch domain of KEAP1 using structure-based drug design methods.

Hepatic oleate regulates one-carbon metabolism during high carbohydrate feeding.

Obesity is a major risk factor for type 2 diabetes, coronary heart disease, and strok. These diseases are associated with profound alterations in gene expression in metabolic tissues. Epigenetic-mediated regulation of gene expression is one mechanism through which environmental factors, such as diet, modify gene expression and disease predisposition.

Cytological Changes and Immunocytochemistry Expression of P53 in Oral Mucosa Among Waterpipe Users in the Kingdom of Saudi Arabia.

Objective In this study, we aimed to assess cytological changes and p53 expression in oral mucosa among waterpipe users in the Kingdom of Saudi Arabia (KSA). Methodology A case-control study was conducted in KSA from January to October 2022. Two cytologic oral smear samples each were taken from 500 volunteers; 300 were waterpipe users (case) while 200 did not use a waterpipe (control).

Hepatic Oleate Regulates Insulin-like Growth Factor-Binding Protein 1 Partially through the mTORC1-FGF21 Axis during High-Carbohydrate Feeding.

Stearoyl-CoA desaturase-1 (SCD1) catalyzes the rate-liming step of monounsaturated fatty acid biosynthesis and is a key regulator of systemic glucose metabolism. Mice harboring either a global (GKO) or liver-specific deletion (LKO) of display enhanced insulin signaling and whole-body glucose uptake. Additionally, GKO and LKO mice are protected from high-carbohydrate diet-induced obesity.

Effect of extracorporeal shock wave therapy on spastic equinus foot in children with unilateral cerebral palsy.

Objectives: This study aims to investigate the effects of radial extracorporeal shock wave therapy on selective motor control, spasticity, gross motor function, and balance in children with unilateral cerebral palsy.

Methods: This randomised controlled study recruited 34 children aged 7-9 with spastic unilateral cerebral palsy. They were randomly allocated to either the control or study group.

Large Pleural Lipoma Manifesting With Chronic Shoulder Pain.

Musculoskeletal symptoms related to orthopedic conditions are highly prevalent worldwide and are a leading cause of morbidity. However, non-orthopedic conditions may also present with musculoskeletal symptoms. For example, shoulder pain may be caused by gastrointestinal, hepatobiliary, cardiac, and neurological pathologies.

Identification of Substituted Amino Acid Hydrazides as Novel Anti-Tubercular Agents, Using a Scaffold Hopping Approach.

Discovery and development of new therapeutic options for the treatment of () infection, particularly drug-resistant strains, are urgently required to tackle the global burden of this disease. Herein, we reported the synthesis of a novel series of N-substituted amino acid hydrazides, utilising a scaffold hopping approach within a library of anti-tubercular agents. Efficacy and selectivity were evaluated against three strains of (wild-type, isoniazid-resistant and rifampicin-resistant), and cytotoxicity against macrophages .

Hepatic stearoyl CoA desaturase 1 deficiency increases glucose uptake in adipose tissue partially through the PGC-1α-FGF21 axis in mice.

Increased carbohydrate consumption increases hepatic lipogenesis, which has been linked to the development of chronic metabolic diseases, including obesity, hepatic steatosis, and insulin resistance. Stearoyl CoA desaturase 1 (SCD1) is a critical lipogenic enzyme that catalyzes the synthesis of two monounsaturated fatty acids, oleate and palmitoleate, from the saturated fatty acids stearate and palmitate, respectively. SCD1-deficient mouse models are protected against diet-induced adiposity, hepatic steatosis, and hyperglycemia.

Hepatic Stearoyl-CoA desaturase-1 deficiency-mediated activation of mTORC1- PGC-1α axis regulates ER stress during high-carbohydrate feeding.

Stearoyl CoA desaturase 1 (SCD1) is a key enzyme in lipogenesis as it catalyzes the synthesis of monounsaturated fatty acids (MUFAs), mainly oleate (18:1n9) and palmitoleate (16:1n7) from saturated fatty acids (SFA), stearate (18:0) and palmitate (16:0), respectively. Studies on SCD1 deficiency in mouse models demonstrated beneficial metabolic phenotypes such as reduced adiposity and improved glucose tolerance. Even though, SCD1 represents a potential target to resolve obesity related metabolic diseases; SCD1 deficiency causes endoplasmic reticulum (ER) stress and activates unfolded protein response (UPR).

Identification of Novel Benzoxa-[2,1,3]-diazole Substituted Amino Acid Hydrazides as Potential Anti-Tubercular Agents.

Discovery and development of new therapeutic options for the treatment of () infection are desperately needed to tackle the continuing global burden of this disease and the efficacy and cost limitations associated with current medicines. Herein, we report the synthesis of a series of novel benzoxa-[2,1,3]-diazole substituted amino acid hydrazides in a two-step synthesis and evaluate their inhibitory activity against and selected bacterial strains of clinical importance utilising an end point-determined REMA assay. Alongside this, their potential for undesired cytotoxicity against mammalian cells was assessed employing standard MTT assay methodologies.

Insights into Stearoyl-CoA Desaturase-1 Regulation of Systemic Metabolism.

Stearoyl-coenzyme A desaturase 1 (SCD1) is a central regulator of fuel metabolism and may represent a therapeutic target to control obesity and the progression of related metabolic diseases including type 2 diabetes and hepatic steatosis. SCD1 catalyzes the synthesis of monounsaturated fatty acids (MUFAs), mainly oleate and palmitoleate, which are important in controlling weight gain in response to feeding high carbohydrate diets. In this review, we evaluate the role of SCD1 isoform in the regulation of lipid and glucose metabolism in metabolic tissues.