197,448 results match your criteria studies compounds

Synthesis and biological evaluation of 2-(4-alkoxy-3-cyano)phenylpyrimidine derivatives with 4-amino or 4-hydroxy as a pharmacophore element binding with xanthine oxidase active site.

Bioorg Med Chem 2021 Apr 2;38:116117. Epub 2021 Apr 2.

Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Culture Road, Shenhe District, Shenyang 110016, China. Electronic address:

Xanthine oxidase is the rate-limiting enzyme critical for the synthesis of uric acid, and therefore xanthine oxidase inhibitors are considered as one of the promising therapies for hyperuricemia and gout. In our previous study, series of 2-(4-alkoxy-3-cyano)phenyl-6-oxo-1,6-dihydropyrimidine-5-carboxylic acids and 2-(4-alkoxy-3-cyano)phenyl-6-imino-1,6-dihydropyrimidine-5-carboxylic acids were synthesized that presented excellent in vitro xanthine oxidase inhibitory potency. Interestingly, molecular docking studies revealed that the interaction behavior of these compounds with xanthine oxidase was changed after the conversion from a hydroxy group to amine group. Read More

View Article and Full-Text PDF

Flavonoid-triazolyl hybrids as potential anti-hepatitis C virus agents: Synthesis and biological evaluation.

Eur J Med Chem 2021 Mar 31;218:113395. Epub 2021 Mar 31.

Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. Electronic address:

A series of flavonoid-triazolyl hybrids were synthesized and evaluated as novel inhibitors of hepatitis C virus (HCV). The results of anti-HCV activity assays showed that most of the synthesized derivatives at a concentration of 100 μg/mL inhibited the generation of progeny virus. Among these derivatives, 10m and 10r exhibited the most potent anti-HCV activity and inhibited the production of HCV in a dose-dependent manner. Read More

View Article and Full-Text PDF

Antiviral zinc oxide nanoparticles mediated by hesperidin and in silico comparison study between antiviral phenolics as anti-SARS-CoV-2.

Colloids Surf B Biointerfaces 2021 Mar 26;203:111724. Epub 2021 Mar 26.

Department of Phytochemistry and Plant Systematics, Pharmaceutical Division, National Research Centre, Dokki, Cairo, Egypt. Electronic address:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus (COVID-19), is the virus responsible for over 69,613,607 million infections and over 1,582,966 deaths worldwide. All treatment measures and protocols were considered to be supportive only and not curative. During this current coronavirus pandemic, searching for pharmaceutical or traditional complementary and integrative medicine to assist with prevention, treatment, and recovery has been advantageous. Read More

View Article and Full-Text PDF

Design, synthesis and biological evaluation of anilide (dicarboxylic acid) shikonin esters as antitumor agents through targeting PI3K/Akt/mTOR signaling pathway.

Bioorg Chem 2021 Mar 29;111:104872. Epub 2021 Mar 29.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China. Electronic address:

Triple-negative breast cancer (TNBC) has an unfavorable prognosis attribute to its low differentiation, rapid proliferation and high distant metastasis rate. PI3K/Akt/mTOR as an intracellular signaling pathway plays a key role in the cell proliferation, migration, invasion, metabolism and regeneration. In this work, we designed and synthesized a series of anilide (dicarboxylic acid) shikonin esters targeting PI3K/Akt/mTOR signaling pathway, and assessed their antitumor effects. Read More

View Article and Full-Text PDF

Novel 1,2,4-oxadiazole-chalcone/oxime hybrids as potential antibacterial DNA gyrase inhibitors: Design, synthesis, ADMET prediction and molecular docking study.

Bioorg Chem 2021 Apr 1;111:104885. Epub 2021 Apr 1.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, 82524 Sohag, Egypt. Electronic address:

New antibacterial drugs are urgently needed to tackle the rapid rise in multi-drug resistant bacteria. DNA gyrase is a validated target for the development of new antibacterial drugs. Thus, in the present investigation, a novel series of 1,2,4-oxadiazole-chalcone/oxime (6a-f) and (7a-f) were synthesized and characterized by IR, NMR (H and C) and elemental analyses. Read More

View Article and Full-Text PDF

Occurrence of parabens in outdoor environments: Implications for human exposure assessment.

Environ Pollut 2021 Apr 1;282:117058. Epub 2021 Apr 1.

International Joint Research Center for Persistent Toxic Substances (IJRC-PTS), State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150090, China; Heilongjiang Provincial Key Laboratory of Polar Environment and Ecosystem (HPKL-PEE), Harbin, 150090, China. Electronic address:

Parabens (PBs) are widely used as preservatives in food, pharmaceuticals and personal care products (PCPs). Due to their potential characteristics, similar to endocrine-disrupting compounds, their safety in our daily products and frequent exposure to human health have become public concerns. Nevertheless, little information is available about the occurrence of PBs in outdoor environments and their implications for human exposure. Read More

View Article and Full-Text PDF

Characteristics and sources of non-methane VOCs and their roles in SOA formation during autumn in a central Chinese city.

Sci Total Environ 2021 Mar 27;782:146802. Epub 2021 Mar 27.

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China; State Environmental Protection Key Laboratory of Sources and Control of Air Pollution Complex, Tsinghua University, Beijing 100084, China.

Volatile organic compounds (VOCs) are essential in secondary organic aerosol (SOA) formation due to their dual roles as precursors and oxidant producers. In order to explore the dominant contributions of SOA formation from VOCs in central China, 53 VOC species were observed with proton transfer reaction-mass spectrometry (PTR-MS) and canister grab samples in Xinxiang, a mid-sized city located in Henan Province, from November 5th to December 3rd, 2018. The result showed that anthropogenic emissions were intensive compared with many studies in the world. Read More

View Article and Full-Text PDF

Regulation of Nuclear Factor-KappaB (NF-κB) signaling pathway by non-coding RNAs in cancer: Inhibiting or promoting carcinogenesis?

Cancer Lett 2021 Apr 7. Epub 2021 Apr 7.

NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117 600, Singapore. Electronic address:

The nuclear factor-kappaB (NF-κB) signaling pathway is considered as a potential therapeutic target in cancer therapy. It has been well established that transcription factor NF-κB is involved in regulating physiological and pathological events including inflammation, immune response and differentiation. Increasing evidences suggest that deregulated NF-κB signaling can enhance cancer cell proliferation, metastasis and also mediate radio-as well as chemo-resistance. Read More

View Article and Full-Text PDF

Automated blood sampling in canine telemetry studies: Enabling enhanced assessments of cardiovascular liabilities and safety margins.

J Pharmacol Toxicol Methods 2021 Apr 7:107066. Epub 2021 Apr 7.

AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America.

Introduction: A successful integration of automated blood sampling (ABS) into the telemetry instrumented canine cardiovascular model is presented in this study. This combined model provides an efficient means to quickly gain understanding of potential effects on key cardiovascular parameters in dog while providing a complete Pharmacokinetic/Pharmacodynamic (PK/PD) profile for discovery compounds without handling artifacts, reducing the need for a separate pharmacokinetic study.

Methods: Male beagle dogs were chronically implanted with telemetry devices (PhysioTel™ model D70-PCTP) and vascular access ports (SPMID-GRIDAC-5NC). Read More

View Article and Full-Text PDF

Meet me halfway: Are in vitro 3D cancer models on the way to replace in vivo models for nanomedicine development?

Adv Drug Deliv Rev 2021 Apr 7. Epub 2021 Apr 7.

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address:

The complexity and diversity of the biochemical processes that occur during tumorigenesis and metastasis are frequently over-simplified in the traditional in vitro cell cultures. Two-dimensional cultures limit researchers' experimental observations and frequently give rise to misleading and contradictory results. Therefore, in order to overcome the limitations of in vitro studies and bridge the translational gap to in vivo applications, 3D models of cancer cell were developed in the last decades. Read More

View Article and Full-Text PDF

Investigation of angucycline compounds as potential drug candidates against SARS Cov-2 main protease using docking and molecular dynamic approaches.

Mol Divers 2021 Apr 10. Epub 2021 Apr 10.

Department of Chemistry, Dicle University, 21280, Diyarbakir, Turkey.

The emerged Coronavirus disease (COVID-19) causes severe or even fatal respiratory tract infection, and to date there is no FDA-approved therapeutics or effective treatment available to effectively combat this viral infection. This urgent situation is an attractive research area in the field of drug design and development. One of the most important targets of SARS-coronavirus-2 (SARS Cov-2) is the main protease (3CLpro). Read More

View Article and Full-Text PDF

Can seafood from marine sites of dumped World War relicts be eaten?

Arch Toxicol 2021 Apr 10. Epub 2021 Apr 10.

Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Campus Kiel, Brunswiker Str. 10, 24105, Kiel, Germany.

Since World War I, considerable amounts of warfare materials have been dumped at seas worldwide. After more than 70 years of resting on the seabed, reports suggest that the metal shells of these munitions are corroding, such that explosive chemicals leak out and distribute in the marine environment. Explosives such as TNT (2,4,6-trinitrotoluene) and its derivatives are known for their toxicity and carcinogenicity, thereby posing a threat to the marine environment. Read More

View Article and Full-Text PDF

An ultrafast and flexible LC-MS/MS system paves the way for machine learning driven in vivo sample processing and data evaluation in early drug discovery.

Rapid Commun Mass Spectrom 2021 Apr 9:e9096. Epub 2021 Apr 9.

Boehringer Ingelheim Pharma GmbH & Co. KG, Drug Discovery Sciences, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.

Rationale: Low speed and low flexibility of most LC-MS/MS approaches in early drug discovery delay sample analysis from routine in vivo studies within the same day. A high-throughput platform for the rapid quantification of drug compounds in various in vivo assays was developed and established in routine bioanalysis.

Methods: Automated selection of an efficient and adequate LC method was realized by autonomous sample qualification for ultrafast batch gradients (9 s/sample) or for fast linear gradients (45 s/sample) if samples required chromatography. Read More

View Article and Full-Text PDF

Universal Toxicity Gene Signatures for Early Identification of Drug-Induced Tissue Injuries in Rats.

Toxicol Sci 2021 Apr 9. Epub 2021 Apr 9.

Safety Assessment and Laboratory Animal Resources, Merck & Co., Inc., West Point, PA, 19486, USA.

A new safety testing paradigm that relies on gene expression biomarker panels was developed to easily and quickly identify drug-induced injuries across tissues in rats prior to drug candidate selection. Here we describe the development, qualification, and implementation of gene expression signatures that diagnose tissue degeneration/necrosis for use in early rat safety studies. Approximately 400 differentially expressed genes were first identified that were consistently regulated across 4 prioritized tissues (liver, kidney, heart, skeletal muscle), following injuries induced by known toxicants. Read More

View Article and Full-Text PDF

Characterization of Naturally Occurring Alpha-Diketone Emissions and Exposures at a Coffee Roasting Facility and Associated Retail Café.

Ann Work Expo Health 2021 Apr 10. Epub 2021 Apr 10.

Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.

Background: Alpha-diketones such as diacetyl and 2,3-pentanedione have been used as artificial flavorings in a variety of industries and are produced naturally when food products such as coffee beans are roasted. Exposure to these compounds has been associated with bronchiolitis obliterans, a rare and severe respiratory disease. In the current paper, we (i) evaluate which steps in the coffee production process are associated with the highest alpha-diketone emissions at a small craft coffee roaster and associated café, (ii) determine the extent to which direct-reading measurements of CO, CO2, and total volatile organic compounds (VOCs) can serve as lower-cost surrogate indicators for diacetyl concentrations, and (iii) conduct a limited emissions study to quantify the effect that the process variable of roast type has on diacetyl emissions from grinding beans. Read More

View Article and Full-Text PDF

Tuning the reactivity of alkoxyl radicals from 1,5-hydrogen atom transfer to 1,2-silyl transfer.

Nat Commun 2021 Apr 9;12(1):2131. Epub 2021 Apr 9.

The Institute for Advanced Studies, Engineering Research Center of Organosilicon Compounds and Materials, Ministry of Education, Wuhan University, Wuhan, People's Republic of China.

Controlling the reactivity of reactive intermediates is essential to achieve selective transformations. Due to the facile 1,5-hydrogen atom transfer (HAT), alkoxyl radicals have been proven to be important synthetic intermediates for the δ-functionalization of alcohols. Herein, we disclose a strategy to inhibit 1,5-HAT by introducing a silyl group into the α-position of alkoxyl radicals. Read More

View Article and Full-Text PDF

Determinants of phthalate exposure among a U.S.-based group of Latino workers.

Int J Hyg Environ Health 2021 Apr 6;234:113739. Epub 2021 Apr 6.

Johns Hopkins University, Bloomberg School of Public Health, Department of Environmental Health & Engineering, Baltimore, MD, USA; Maryland Institute of Applied Environmental Health, School of Public Health, University of Maryland, College Park, MD, USA. Electronic address:

Background: Phthalates are endocrine disrupting compounds linked to various adverse health effects. U.S. Read More

View Article and Full-Text PDF

Synthesis and anti-inflammatory activity of novel steroidal chalcones with 3β-pregnenolone ester derivatives in RAW 264.7 cells in vitro.

Steroids 2021 Apr 6:108830. Epub 2021 Apr 6.

Department of Pharmacology, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address:

To identify new potential anti-inflammatory agents, we herein report the synthesis of novel steroidal chalcones with 3β-pregnenolone esters of cinnamic acid derivatives using pregnenolone as the starting material. The structures of the newly synthesised compounds were confirmed by H-NMR, C-NMR, HRMS and infrared imaging. All the derivatives were examined to determine their in vitro anti-inflammatory profiles against LPS-induced inflammation in RAW 264. Read More

View Article and Full-Text PDF

Asynchronous Bilateral Achilles Tendon Rupture with Selective Androgen Receptor Modulators: A Case Report.

JBJS Case Connect 2021 Apr 9;11(2). Epub 2021 Apr 9.

Department of Orthopaedic Surgery, MedStar Union Memorial Hospital, Baltimore, Maryland.

Case: A 36-year-old male competitive powerlifter sustained asynchronous bilateral Achilles tendon ruptures after using 2 types of selective androgen receptor modulators (SARMs). Both tendon ruptures occurred near the myotendinous junction and were treated with open surgical repair and an initial period of immobilization followed by progressive weightbearing and rehabilitation; no postoperative complications were observed.

Conclusion: Previous studies have reported that anabolic androgenic steroids have a deleterious impact on tendon structure and function. Read More

View Article and Full-Text PDF

Targeting Chikungunya Virus Replication by Benzoannulene Inhibitors.

J Med Chem 2021 Apr 9. Epub 2021 Apr 9.

Drug Discovery Division, Southern Research, 2000 Ninth Avenue South, Birmingham, Alabama 35205, United States.

A benzo[6]annulene, 4-(-butyl)--(3-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl) benzamide (), was identified as an inhibitor against Chikungunya virus (CHIKV) with antiviral activity EC = 1.45 μM and viral titer reduction (VTR) of 2.5 log at 10 μM with no observed cytotoxicity (CC = 169 μM) in normal human dermal fibroblast cells. Read More

View Article and Full-Text PDF

Formulation of chitosan coated nanoliposomes for the oral delivery of colistin sulfate: characterization, Tc-radiolabeling and biodistribution studies.

Drug Dev Ind Pharm 2021 Apr 9:1-10. Epub 2021 Apr 9.

Labeled Compounds Department, Hot Lab Center, Egyptian Atomic Energy Authority, Cairo, Egypt.

Colistin sulfate is a very important antibiotic for the treatment of multidrug-resistant Gram-negative infections. Unfortunately, it has low oral bioavailability and several side effects following parenteral administration. The present study aims to develop chitosan-coated colistin nanoliposomes to improve the stability in the gastrointestinal tract and to enhance the oral delivery of colistin. Read More

View Article and Full-Text PDF

Bis(Iminophosphorano)-Substituted Pyridinium Ions and their Corresponding Bispyridinylidene Organic Electron Donors*.

Chemistry 2021 Apr 8. Epub 2021 Apr 8.

University of New Brunswick, Department of Chemistry, P. O. Box 4400, E3B 5A3, Fredericton, CANADA.

Optimized synthetic procedures for pyridinium ions featuring iminophosphorano (-N=PR3 ; R = Ph, Cy) π-donor substituents in the 2- and 4- positions are described. Crystallographic and theoretical studies reveal that the strongly donating substituents severely polarize the π-electrons of the pyridyl ring at the expense of aromaticity. Moreover, the pyridinium ions are readily deprotonated to generate powerful bispyridinylidene (BPY) organic electron donors. Read More

View Article and Full-Text PDF

Activatable F MRI Nanoprobes for Visualization of Biological Targets in Living Subjects.

Adv Mater 2021 Apr 8:e2005657. Epub 2021 Apr 8.

State Key Laboratory of Physical Chemistry of Solid Surfaces, The MOE Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory for Chemical Biology of Fujian Province, and Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.

Visualization of biological targets such as crucial cells and biomolecules in living subjects is critical for the studies of important biological processes. Though H magnetic resonance imaging (MRI) has demonstrated its power in offering detailed anatomical and pathological information, its capacity for in vivo tracking of biological targets is limited by the high biological background of H. F distinguishes itself from its competitors as an exceptional complement to H in MRI through its high sensitivity, low biological background, and broad chemical shift range. Read More

View Article and Full-Text PDF

Studies on Microbial Quality, Protein Yield, and Antioxidant Properties of Some Frozen Edible Insects.

Int J Food Sci 2021 23;2021:5580976. Epub 2021 Mar 23.

Food Science and Technology, Science Division, International College, Mahidol University, Buddhamonthon 4 Rd, Nakhonpathom, Salaya 73170, Thailand.

This research investigated the microbial quality and the protein contents of Thai commercial frozen products of silkworm (), bamboo caterpillar (), and field cricket (). Total mesophilic aerobic counts were about 8-8.4 log cfu/g, while lactic acid bacteria numbers were up to 5. Read More

View Article and Full-Text PDF

Antioxidant, Cytotoxicity and Cytoprotective Potential of Extracts of and Berries.

J Pharmacopuncture 2021 Mar;24(1):24-31

Department of Biological Sciences and Biotechnology, Faculty of Sciences, Botswana International University of Science and Technology, Palapye, Botswana.

Objectives: Accumulation of cellular reactive oxygen species (ROS) leads to oxidative stress. Increased production of ROS, such as superoxide anion, or a deficiency in their clearance by antioxidant defences, mediates cellular pathology. fruits are a source of bioactive compounds and have notable antioxidant activity. Read More

View Article and Full-Text PDF

Review of Pharmacological Properties and Chemical Constituents of .

J Pharmacopuncture 2021 Mar;24(1):14-23

Shahed University of Medical Sciences, Tehran, Iran.

Objectives: (parsnip), is a plant with nutritional and medicinal properties which has been used in all over the world and study about it is rare. In Persian Medicine parsnip is named as and has many uses such as laxative, libido enhancer, kidney stone crusher and diuretic. Because the wide traditional usage of parsnip, in this review the composition and pharmacological properties of this plant are discussed. Read More

View Article and Full-Text PDF

Biological and Therapeutic Effects of Troxerutin: Molecular Signaling Pathways Come into View.

J Pharmacopuncture 2021 Mar;24(1):1-13

Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

Flavonoids consist a wide range of naturally occurring compounds which are exclusively found in different fruits and vegetables. These medicinal herbs have a number of favourable biological and therapeutic activities such as antioxidant, neuroprotective, renoprotective, anti-inflammatory, anti-diabetic and anti-tumor. Troxerutin, also known as vitamin P4, is a naturally occurring flavonoid which is isolated from tea, coffee and cereal grains as well as vegetables. Read More

View Article and Full-Text PDF

Species as Sources of Active Phytochemicals for Dermatological and Cosmetic Applications.

Oxid Med Cell Longev 2021 25;2021:6643827. Epub 2021 Mar 25.

Department of Pharmacognosy, Medical University of Lublin, Chodźki 1, 20-093, Poland.

spp. is well known for its broad range of applications and long history of use in traditional medicine around the world. Health benefits of extracts result from the multitude of secondary metabolites identified in the plants from this genus that include flavonoids, phenolic acids, terpenes, guaianolides, phytosterols, fatty acids, and organic acids. Read More

View Article and Full-Text PDF

Interactive Effects of Mycorrhizae, Soil Phosphorus, and Light on Growth and Induction and Priming of Defense in .

Front Plant Sci 2021 23;12:647372. Epub 2021 Mar 23.

Department of Terrestrial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, Netherlands.

Increasing demands to reduce fertilizer and pesticide input in agriculture has triggered interest in arbuscular mycorrhizal fungi (AMF) that can enhance plant growth and confer mycorrhiza-induced resistance (MIR). MIR can be based on a variety of mechanisms, including induction of defense compounds, and sensitization of the plant's immune system (priming) for enhanced defense against later arriving pests or pathogens signaled through jasmonic acid (JA). However, growth and resistance benefits of AMF highly depend on environmental conditions. Read More

View Article and Full-Text PDF

Amino Acid Conjugates of Aminothiazole and Aminopyridine as Potential Anticancer Agents: Synthesis, Molecular Docking and in vitro Evaluation.

Drug Des Devel Ther 2021 1;15:1459-1476. Epub 2021 Apr 1.

State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People's Republic of China.

Purpose: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate this therapeutic failure. The current study demonstrated the synthesis of 2-aminothiazole [() and ()] and 2-aminopyridine [() and ()] derivatives that can target multiple cellular networks implicated in cancer development.

Methods: Biological assays were performed to investigate the antioxidant and anticancer potential of synthesized compounds. Read More

View Article and Full-Text PDF