348,788 results match your criteria potent antagonists


Cytotoxicity and Antiviral Activities of Haplophyllum tuberculatum Essential Oils, Pure Compounds, and Their Combinations against Coxsackievirus B3 and B4.

Planta Med 2021 Jul 22. Epub 2021 Jul 22.

Department of Analytical Chemistry, Applied Chemometrics and Molecular Modelling (FABI), Center for Pharmaceutical Research (CePhaR), Vrije Universiteit Brussel (VUB), Belgium.

is a plant commonly used in folk medicine to treat several diseases including vomiting, nausea, infections, rheumatism, and gastric pains. In the current study, essential oils, hydrosols, the pure compounds -(+)-limonene, -(-)-limonene, and 1-octanol, as well as their combinations -(+)-limonene/1-octanol and -(-)-limonene/1-octanol, were screened for their cytotoxicity on HEp-2 cells after 24, 48, and 72 h, and then tested for their activity against Coxsackievirus B3 and B4 (CV-B3 and CV-B4) at 3 different moments: addition of the plant compounds before, after, or together with virus inoculation. Results showed that the samples were more cytotoxic after 72 h than after 24 h or 48 h cell contact. Read More

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Suffrutines A and B Inhibit the Expression of Inflammatory Mediators in LPS-Induced RAW264.7 Cells by Suppressing the NF-κB Signaling Pathway.

Planta Med 2021 Jul 22. Epub 2021 Jul 22.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China.

is a traditional Chinese medicine that has been commonly used for the treatment of inflammatory ailments, including rheumatism and lumbago. Suffrutines A and suffrutines B are a pair of novel E,E and Z,E isomeric indolizidine alkaloids isolated from the roots of . However, their anti-inflammatory activity has not been reported thus far. Read More

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Enhancing enzymatic performance with nanoparticle immobilization: improved analytical and control capability for synthetic biochemistry.

Curr Opin Biotechnol 2021 Jul 19;71:77-90. Epub 2021 Jul 19.

Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, D.C., 20375, USA. Electronic address:

Enzymes are incredibly potent catalysts with the potential for rapid turnover rates and exquisite specificity, leading to their desired use in multiple biotechnological processes. Yet using these natural catalysts outside of their evolved role can necessitate significant engineering. Immobilization onto microscale (or larger) scaffolds can impart industrially-desired properties but often sacrifices enzymatic activity for long-term stability; in contrast, nanoparticle (NP) conjugation of enzymes can preserve or even enhance their activity. Read More

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Onion component, isoalliin, stimulates feeding and activates the arcuate nucleus neuropeptide Y, ghrelin- and Ninjin'yoeito-responsive neurons.

Neuropeptides 2021 Jul 10;89:102180. Epub 2021 Jul 10.

Center for Integrative Physiology, Division of Integrative Physiology, Kansai Electric Power Medical Research Institute, 1-5-6 Minatojimaminamimachi, Chuou-ku, Kobe 650-0047, Japan; Division of Diabetes, Metabolism and Endocrinology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, Japan; Pharmacological Department of Herbal Medicine, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima 890-8544, Japan. Electronic address:

Appetite loss or anorexia substantially decreases the quality of life in patients with cancer, depression and gastrointestinal disorders, and can lead to sarcopenia and frailty. Foods that restore appetite have been sought-for but are not currently available. Historically, onion intake was adopted to treat a variety of diseases with reduced appetite including cancer and gastrointestinal disturbances. Read More

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Investigation of nanoplastic cytotoxicity using SH-SY5Y human neuroblastoma cells and polystyrene nanoparticles.

Toxicol In Vitro 2021 Jul 19:105225. Epub 2021 Jul 19.

Environmental Symbiotic System Major, Nippon Institute of Technology, 4-1, Gakuendai, Miyashiro, Minami-saitama, Saitama 345-8501, Japan.

Nanoplastics have spread widely throughout not only the oceans but also the atmosphere, and recently created great concern about human health relevant to ingestion and accumulation of the nanoparticles by aquatic organisms in the human food-chain. However, how the nanoplastics have an affect on actual human body remains largely unknown, and in particular, little knowledge about nanoplastic exposure to the nervous system in human has been obtained in vitro and still less vivo. Here, we evaluated how much concentration of nanoplastics had a direct impact on cells in the nervous system as the fundamental information. Read More

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Design and evaluation of GLP-1 receptor G-protein biased agonist with prolonged efficacy on diabetes.

Life Sci 2021 Jul 19:119844. Epub 2021 Jul 19.

Peking University Third Hospital, Beijing 100191, PR China. Electronic address:

Aim: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potent drug development target for treating diabetes and obesity. Here, we designed and evaluated novel long-acting GLP-1R G protein biased agonist with potent clinical application.

Main Methods: GLP-1R G-protein biased sequences were screened via a high-throughput autocrine-based strategy and then fused to Exendin (9-39). Read More

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Predicting mutant outcome by combining deep mutational scanning and machine learning.

Proteins 2021 Jul 22. Epub 2021 Jul 22.

Department of Computer Science, Ben-Gurion University of the Negev, Be'er Sheva, Israel.

Motivation: Deep mutational scanning provides unprecedented wealth of quantitative data regarding the functional outcome of mutations in proteins. A single experiment may measure properties (e.g. Read More

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A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site.

PLoS Pathog 2021 Jul 22;17(7):e1009671. Epub 2021 Jul 22.

Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, United States of America.

Allosteric integrase inhibitors (ALLINIs) are a class of experimental anti-HIV agents that target the noncatalytic sites of the viral integrase (IN) and interfere with the IN-viral RNA interaction during viral maturation. Here, we report a highly potent and safe pyrrolopyridine-based ALLINI, STP0404, displaying picomolar IC50 in human PBMCs with a >24,000 therapeutic index against HIV-1. X-ray structural and biochemical analyses revealed that STP0404 binds to the host LEDGF/p75 protein binding pocket of the IN dimer, which induces aberrant IN oligomerization and blocks the IN-RNA interaction. Read More

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Molecular and physiological characterization of Fusarium strains associated with different diseases in date palm.

PLoS One 2021 22;16(7):e0254170. Epub 2021 Jul 22.

Department of Plant Protection, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia.

Several species of Fusarium cause serious diseases in date palm worldwide. In the present work, 14 SSR markers were used to assess the genetic variation of Fusarium strains isolated from diseased trees in Saudi Arabia. We also studied the effect of different temperatures on mycelial growth of these strains. Read More

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SOCS3 deficiency in cardiomyocytes elevates sensitivity of ischemic preconditioning that synergistically ameliorates myocardial ischemia reperfusion injury.

PLoS One 2021 22;16(7):e0254712. Epub 2021 Jul 22.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.

Ischemic preconditioning (IPC) is the most powerful endogenous cardioprotective form of cellular adaptation. However, the inhibitory or augmenting mechanism underlying cardioprotection via IPC remains largely unknown. Suppressor of cytokine signaling-3 (SOCS3) is a cytokine-inducible potent negative feedback regulator of the signal transducer and activator of transcription-3 (STAT3) signaling pathway. Read More

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Inhalable nanocatchers for SARS-CoV-2 inhibition.

Proc Natl Acad Sci U S A 2021 Jul 2;118(29). Epub 2021 Jul 2.

Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China;

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Read More

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Ferroptosis-Strengthened Metabolic and Inflammatory Regulation of Tumor-Associated Macrophages Provokes Potent Tumoricidal Activities.

Nano Lett 2021 Jul 22. Epub 2021 Jul 22.

School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, People's Republic of China.

Modulation of tumor-associated macrophages (TAMs) holds promise for cancer treatment, mainly relying on M1 signaling activation and pro-inflammatory promotion. Nevertheless, the antitumor activity is often limited by the anti-inflammatory factors in the tumor microenvironment. Moreover, the metabolic function of TAMs is also critical to tumor progression. Read More

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Synthesis of Aristoquinoline Enantiomers and Their Evaluation at the α3β4 Nicotinic Acetylcholine Receptor.

Org Lett 2021 Jul 22. Epub 2021 Jul 22.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.

The first synthesis of aristoquinoline (), a naturally occurring nicotinic acetylcholine receptor (nAChR) antagonist, was accomplished using two different approaches. Comparison of the synthetic material's spectroscopic data to that of the isolated alkaloid identified a previously misassigned stereogenic center. An evaluation of each enantiomer's activity at the α3β4 nAChR revealed that (+)- is significantly more potent than (-)-. Read More

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Structural Insights into Notum Covalent Inhibition.

J Med Chem 2021 Jul 22. Epub 2021 Jul 22.

Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, U.K.

The carboxylesterase Notum hydrolyzes a palmitoleate moiety from Wingless/Integrated(Wnt) ligands and deactivates Wnt signaling. Notum inhibitors can restore Wnt signaling which may be of therapeutic benefit for pathologies such as osteoporosis and Alzheimer's disease. We report the identification of a novel class of covalent Notum inhibitors, 4-(indolin-1-yl)-4-oxobutanoate esters. Read More

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Discovery of IACS-9779 and IACS-70465 as Potent Inhibitors Targeting Indoleamine 2,3-Dioxygenase 1 (IDO1) Apoenzyme.

J Med Chem 2021 Jul 22. Epub 2021 Jul 22.

IACS (Institute for Applied Cancer Science), University of Texas, MD Anderson Cancer Center, 1881 East Road, Houston, Texas 77054, United States.

Indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme that mediates the rate-limiting step in the metabolism of l-tryptophan to kynurenine, has been widely explored as a potential immunotherapeutic target in oncology. We developed a class of inhibitors with a conformationally constrained bicyclo[3.1. Read More

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Neo-clerodane Diterpenoids with Hypoglycemic Effects in Vivo from the Aerial Parts of Salvia hispanica L.

Chem Biodivers 2021 Jul 22. Epub 2021 Jul 22.

Kunming Institute of Botany, Chinese Academy of Sciences, State Key Laboratory of Phytochemistry and Plant Resources in West China, 132 Lanhei Road, Heilongtan, Kunming 650201, Not Available, 650201, Kunming, CHINA.

A new neo -clerodane diterpenoid, salvihispin H ( 1 ), and six known ones ( 2 - 7 ) were identified from the aerial parts of Salvia hispanica L. The structure and absolute configuration of 1 were elucidated by extensive analysis of spectroscopic ( 1 H, 13 C, and 2D NMR, and HRESIMS) and single-crystal X-ray diffraction data. The anti-diabetic effects of salvihispin H ( 1 ) and salvifaricin ( 2 ) were evaluated in diabetic db/db mice. Read More

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Selective obstruction of the mTORC2 complex by a naturally occurring cholestane saponin (OSW-1) for inhibiting prostate cancer cell growth.

Authors:
Ahmed Elgehama

J Asian Nat Prod Res 2021 Jul 22:1-10. Epub 2021 Jul 22.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.

Ait (OCA) is a natural product used in Chinese traditional medicine. The cholestane saponin OSW-1 is isolated from plant OCA and has recently been shown to have potent cytotoxic effects against different types of cancers. The therapeutic efficacy of OSW-1 on prostate cancer and its underlying mechanism are yet to be established. Read More

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A comparison study between dimethyl itaconate and dimethyl fumarate in electrophilicity, Nrf2 activation, and anti-inflammation .

J Asian Nat Prod Res 2021 Jul 22:1-12. Epub 2021 Jul 22.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

Dimethyl itaconate (DMI) is an analog of dimethyl fumarate (DMF), an approved NF-E2-related Factor 2 (Nrf2) activator for multiple sclerosis. This study evaluated the potential of DMI as an anti-inflammatory agent by comparing DMI with DMF in electrophilicity, Nrf2 activation, and anti-inflammation . The results showed that DMI was less electrophilic but better at inducing a durable activation of Nrf2 when compared with DMF. Read More

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Long-Term Fertilization Alters Nitrous Oxide Cycling Dynamics in Salt Marsh Sediments.

Environ Sci Technol 2021 Jul 22. Epub 2021 Jul 22.

Department of Geosciences, Princeton University, Princeton 08544, New Jersey, United States.

Salt marsh sediments are known hotspots for nitrogen cycling, including the production and consumption of nitrous oxide (NO), a potent greenhouse gas and ozone-depleting agent. Coastal eutrophication, particularly elevated nitrogen loading from the application of fertilizers, is accelerating nitrogen cycling processes in salt marsh sediments. Here, we examine the impact of long-term fertilization on nitrogen cycling processes with a focus on NO dynamics in a New England salt marsh. Read More

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Sorafenib for hepatocellular carcinoma: potential molecular targets and resistance mechanisms.

J Chemother 2021 Jul 22:1-16. Epub 2021 Jul 22.

Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, India.

Hepatocellular carcinoma (HCC) is the most widespread typical therapy-resistant, unresectable type of malignant solid tumour with a high death rate constituting huge medical concern. Sorafenib is a small molecule oral multi-target kinase potent inhibitor that acts by suppressing/blocking the multiplication of the tumour cells, angiogenesis, and encouraging apoptosis of the tumour cells. Though, the precise mechanism of tumour cell death induction by sorafenib is yet under exploration. Read More

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Design, Synthesis, and Characterization of 4-Aminoquinazolines as Potent Inhibitors of the G Protein-Coupled Receptor Kinase 6 (GRK6) for the Treatment of Multiple Myeloma.

J Med Chem 2021 Jul 22. Epub 2021 Jul 22.

Princess Margaret Cancer Centre, Toronto Medical Discovery Tower, 101 College Street, Room 12-306, Toronto, Ontario M5G 1L7, Canada.

Both previous and additional genetic knockdown studies reported herein implicate G protein-coupled receptor kinase 6 (GRK6) as a critical kinase required for the survival of multiple myeloma (MM) cells. Therefore, we sought to develop a small molecule GRK6 inhibitor as an MM therapeutic. From a focused library of known kinase inhibitors, we identified two hits with moderate biochemical potencies against GRK6. Read More

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Functional dissection and modulation of the BirA protein for improved autotrophic growth of gas-fermenting Clostridium ljungdahlii.

Microb Biotechnol 2021 Jul 21. Epub 2021 Jul 21.

Key Laboratory of Synthetic Biology, The State Key Laboratory of Plant Carbon-Nitrogen Assimilation, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, 200032, China.

Gas-fermenting Clostridium species can convert one-carbon gases (CO /CO) into a variety of chemicals and fuels, showing excellent application prospects in green biological manufacturing. The discovery of crucial genes and proteins with novel functions is important for understanding and further optimization of these autotrophic bacteria. Here, we report that the Clostridium ljungdahlii BirA protein (ClBirA) plays a pleiotropic regulator role, which, together with its biotin protein ligase (BPL) activity, enables an effective control of autotrophic growth of C. Read More

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Potential of nafimidone derivatives against co-morbidities of epilepsy: In vitro, in vivo, and in silico investigations.

Drug Dev Res 2021 Jul 22. Epub 2021 Jul 22.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.

Nafimidone is known for its clinical antiepileptic effects and alcohol derivatives of nafimidone were reported be potent anticonvulsants. These compounds are structurally similar to miconazole, which is known to inhibit cholinesterases, protect neurons, and ameliorate cognitive decline. Herein, we aimed to reveal the potential of three nafimidone alcohol esters (5 g, 5i, and 5 k), which were previously reported for their anticonvulsant effects, against co-morbidities of epilepsy such as inflammatory and neuropathic pain, cognitive and behavioral deficits, and neuron death, and understand their roles in related pathways such as γ-butyric acid type A (GABA ) receptor and cholinesterases using in vitro, in vivo and in silico methods. Read More

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Development of EQ-6, a Novel Analogue of Ethoxyquin to Prevent Chemotherapy-Induced Peripheral Neuropathy.

Neurotherapeutics 2021 Jul 21. Epub 2021 Jul 21.

School of Medicine, Johns Hopkins University, 855 N. Wolfe St., Suite 248, Baltimore, MD, 21205, USA.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and often dose-limiting side effect of many cancer drugs. Because the onset of neuronal injury is known, it is an ideal clinical target to develop neuroprotective strategies. Several years ago, we had identified ethoxyquin as a potent neuroprotective drug against CIPN through a phenotypic drug screening and demonstrated a novel mechanism of action, inhibition of chaperone domain of heat shock protein 90. Read More

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Low-molecular weight chitosan enhances antibacterial effect of antibiotics and permeabilizes cytoplasmic membrane of Staphylococcus epidermidis biofilm cells.

Folia Microbiol (Praha) 2021 Jul 21. Epub 2021 Jul 21.

Department of Biotechnology, University of Chemistry and Technology in Prague, Technická 5, Prague 6 - Dejvice 166 28, Prague, Czech Republic.

This study evaluated the effect of low-molecular weight chitosan on Staphylococcus epidermidis, a common colonizer of joint implants and other prosthetic devices. We have also attempted to elucidate its mechanism of action. Chitosan was found to be effective against both the planktonic and biofilm cells (MIC 35-40 mg/L; MBIC 40-150 mg/L), in contrast to the antibiotics erythromycin and tetracycline with no antibiofilm activity (MBIC not found). Read More

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Screening of Natural Phytocompounds Towards Identification of Potential Lead Compounds to Treat COVID-19.

Front Mol Biosci 2021 5;8:637122. Epub 2021 Jul 5.

Bioscience Research Foundation, Chennai, India.

COVID-19 is one of the members of the coronavirus family that can easily assail humans. As of now, 10 million people are infected and above two million people have died from COVID-19 globally. Over the past year, several researchers have made essential advances in discovering potential drugs. Read More

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New mechanistic insights into hepatoprotective activity of milk thistle and chicory quantified extract: The role of hepatic Farnesoid-X activated receptors.

Avicenna J Phytomed 2021 Jul-Aug;11(4):367-379

Department of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.

Objective: Farnesoid-X-activated receptors (FXR) are key modulators of liver regeneration. Milk thistle and Chicory are known as potent protective remedies in several liver disorders. The objective of this work was to examine the role of in the hepato-healing properties of milk thistle (MTE) and chicory extracts (CE) in a rat model of acetaminophen-induced hepatotoxicity. Read More

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January 2020

Hypoglycemic, hypolipidemic and hepato-protective effect of bee bread in streptozotocin-induced diabetic rats.

Avicenna J Phytomed 2021 Jul-Aug;11(4):343-352

Laboratory of Natural Substances, Pharmacology, Environment, Modeling, Health and Quality of life (SNAMOPEQ), Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Objective: This study aims to shed a new light on pharmacological effects of bee bread as a product of the hive through examination of the effect of itsethyl acetate extract onhyperglycemia, dyslipidemia, and liver dysfunction induced by streptozotocin.

Materials And Methods: The bee bread ethyl acetate extract was analyzed for total phenolics, flavonoids, and the antioxidant activities using total antioxidant capacity, 2, 2- diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and reducing power assays. study was carried out on thirty-six rats divided into control or diabetic rats, received daily for 15 days distilled water (10 ml/kg), or ethyl acetate extract of bee bread (100 mg/kg), or glibenclamide (2. Read More

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October 2019

Mutational Frequencies in Mycobacterial gene using GeneXpert/MTB Rif Assay in Rifampicin Resistant patients at a tertiary care setting in Urban Sindh, Pakistan: Analysis from a Five-Year Period.

Pak J Med Sci 2021 Jul-Aug;37(4):1151-1154

Muhammad Yahya Noori, MBBS, Ph. D, MBA, M. Sc. Associate Professor of Microbiology, Department of Pathology, Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan.

Objectives: To assess the mutational frequencies in Mycobacterial gene using GeneXpert/MTB Rif Assay in rifampicin resistant patients during 2013-2017 at a tertiary care setting in Urban Sindh, Pakistan.

Methods: This Retrospective Descriptive Cross-Sectional Study was conducted at the TB laboratories, Ojha Institute of Chest Diseases, Dow University of Health Sciences. The record of 713 positive cases of Rifampicin Resistant Tuberculosis from January 2013 to December 2017 were analysed. Read More

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November 2020

Total Glucosides of Paeony Ameliorate Pristane-Induced Lupus Nephritis by Inducing PD-1 ligands Macrophages Activating IL-4/STAT6/PD-L2 Signaling.

Front Immunol 2021 5;12:683249. Epub 2021 Jul 5.

Section of Immunology & Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China.

Macrophages, a major subset of innate immune cells, are main infiltrating cells in the kidney in lupus nephritis. Macrophages with different phenotypes exert diverse or even opposite effects on the development of lupus nephritis. Substantial evidence has shown that macrophage M2 polarization is beneficial to individuals with chronic kidney disease. Read More

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