60,136 results match your criteria study structure-activity


Betulonic Acid Derivatives Interfering with Human Coronavirus 229E Replication via the nsp15 Endoribonuclease.

J Med Chem 2021 Apr 20. Epub 2021 Apr 20.

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven, 3000 Leuven, Belgium.

To develop antiviral therapeutics against human coronavirus (HCoV) infections, suitable coronavirus drug targets and corresponding lead molecules must be urgently identified. Here, we describe the discovery of a class of HCoV inhibitors acting on nsp15, a hexameric protein component of the viral replication-transcription complexes, endowed with immune evasion-associated endoribonuclease activity. Structure-activity relationship exploration of these 1,2,3-triazolo-fused betulonic acid derivatives yielded lead molecule as a strong inhibitor (antiviral EC: 0. Read More

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Hyphal growth promotion in vitro of the VA mycorrhizal fungus, Gigaspora margarita Becker & Hall, by the activity of structurally specific flavonoid compounds under CO -enriched conditions.

New Phytol 1992 Nov;122(3):461-467

Centre de Recherche en Biologie Forestiere, Faculté de Foresterie et de Gáomatique, Université Laval, Sainte-Foy, Quebec, G1K 7P4, Canada.

Plant phenolic compounds are known to be inducers of virulence genes in plant-pathogen interactions such as those involving Agrobacterium, and flavonoids are known to be inducers or inhibitors of Nod genes in Rhizobium-legume symbiosis. More recent studies suggest that some of these compounds act as molecular signals in the development of vesicular-arbuscular mycorrhizas (VAM). The present study has shown that hyphal growth of the VAM fungus, Gigaspora margarita Becker & Hall, is affected by both stimulatory and inhibitory flavonoids, when applied at 10 μ together with an optimal carbon dioxide enrichment. Read More

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November 1992

Synthesis and structure-activity relationships of hydroxylated and halogenated 2,4-diaryl benzofuro[3,2-b]pyridin-7-ols as selective topoisomerase IIα inhibitors.

Bioorg Chem 2021 Apr 1;111:104884. Epub 2021 Apr 1.

College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea. Electronic address:

The objective of this study was to discover potential topoisomerase (topo) targeting anticancer agents. Novel series of hydroxylated and halogenated(-F, -Cl, and -CF) 2,4-diaryl benzofuro[3,2-b]pyridin-7-ols were systematically designed and synthesized by faster, economic, and environmentally friendly -proline catalyzed and microwave-assisted one pot reaction method. The synthesized compounds were assessed for topo I and IIα inhibitory and anti-proliferative activities. Read More

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An automated framework for compiling and integrating chemical hazard data.

Clean Technol Environ Policy 2020 Mar;22(2):441-458

National Risk Management Research Laboratory, U.S. Environmental Protection Agency, 26 W. Martin Luther King Dr., Cincinnati, OH 45268, USA.

Comparative chemical hazard assessment, which compares hazards for several endpoints across several chemicals, can be used for a variety of purposes including alternatives assessment and the prioritization of chemicals for further assessment. A new framework was developed to compile and integrate chemical hazard data for several human health and ecotoxicity endpoints from public online sources including hazardous chemical lists, Globally Harmonized System hazard codes (H-codes) or hazard categories from government health agencies, experimental quantitative toxicity values, and predicted values using Quantitative Structure-Activity Relationship (QSAR) models. QSAR model predictions were obtained using EPA's Toxicity Estimation Software Tool. Read More

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Brazilian essential oils as source for the discovery of new anti-COVID-19 drug: a review guided by in silico study.

Phytochem Rev 2021 Apr 13:1-20. Epub 2021 Apr 13.

Laboratório de Fitotecnologia, Universidade Federal de Ouro Preto, Ouro Preto, Brazil.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China and its spread worldwide has become one of the biggest health problem due to the lack of knowledge about an effective chemotherapy. Based on the current reality of the SARS-CoV-2 pandemic, this study aimed to make a review literature about potential anti-coronavirus natural compounds guided by an in silico study. In the first step, essential oils from native species found in the Brazilian herbal medicine market and Brazilian species that have already shown antiviral potential were used as source for the literature search and compounds selection. Read More

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Hyperbolic relational graph convolution networks plus: a simple but highly efficient QSAR-modeling method.

Brief Bioinform 2021 Apr 19. Epub 2021 Apr 19.

College of Pharmaceutical Sciences, Zhejiang University.

Accurate predictions of druggability and bioactivities of compounds are desirable to reduce the high cost and time of drug discovery. After more than five decades of continuing developments, quantitative structure-activity relationship (QSAR) methods have been established as indispensable tools that facilitate fast, reliable and affordable assessments of physicochemical and biological properties of compounds in drug-discovery programs. Currently, there are mainly two types of QSAR methods, descriptor-based methods and graph-based methods. Read More

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Diversity-oriented synthesis of cembranoid derivatives as potential anti-inflammatory agents.

Bioorg Chem 2021 Apr 6;111:104887. Epub 2021 Apr 6.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China; Open Studio for Druggability Research of Marine Natural Products, Pilot National Laboratory for Marine Science and Technology (Qingdao), 1 Wenhai Road, Aoshanwei, Jimo, Qingdao, 266237, China. Electronic address:

Eleven novel cembranoid derivatives were designed, synthesized, and evaluated for their inflammation related activities on the basis of our isolated and previously reported anti-inflammatory marine cembranoids. In bioassay, compound 11 displayed the most promising inhibitory effects with IC value of 1.1 μM for the TNF-α inhibitory activity. Read More

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Quantitative analysis of the relationship of derivatization reagents and detection sensitivity of electrospray ionization-triple quadrupole tandem mass spectrometry: Hydrazines as prototypes.

Anal Chim Acta 2021 May 13;1158:338402. Epub 2021 Mar 13.

Department of Chemistry, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430072, PR China. Electronic address:

Chemical derivatization-assisted electrospray ionization-triple quadrupole mass spectrometry (ESI-QqQ-MS) has become an efficient tool for the quantification of low-molecular-weight molecules. Many studies found that the derivatives of the same analytes derivatized by different derivatization reagents with the same reaction group had different detection sensitivity, even under the same conditions of electrospray ionization-mass spectrometry (ESI-MS). This phenomenon was suggested to be caused by the different modifying groups in the derivatization reagents. Read More

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vHTS and 3D-QSAR for the Identification of Novel Phyto-inhibitors of Farnesyltransferase: Validation of Ascorbic Acid inhibition of Farnesyltransferase in an Animal Model of Breast Cancer.

Drug Res (Stuttg) 2021 Apr 16. Epub 2021 Apr 16.

Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria.

Farnesyltransferase (FTase) is a zinc enzyme that has been the subject of attention in anti-cancer research over the past. In this study, phytochemicals from plants were screened for their inhibitory potentials on the human farnesyltransferase. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model for the inhibition of farnesyltransferase was generated and the inhibition of farnesyltransferase by the hit, ascorbic acid was validated in an animal model of breast cancer. Read More

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Efficiency of Gemini surfactant containing semi-rigid spacer as microbial corrosion inhibitor for carbon steel in simulated seawater.

Bioelectrochemistry 2021 Mar 29;140:107809. Epub 2021 Mar 29.

School of Chemical Engineering and Technology, North University of China, Taiyuan 030051, China.

SRB is one of the main bacteria causing marine microbial corrosion. In order to reduce the loss of microbial corrosion, a Gemini surfactant (12-B-12) containing semi-rigid spacer was used to investigate the anti-bacterial and anti-corrosion performances of carbon steel in simulated seawater by weight-loss test, electrochemical method and surface morphology analysis. The results showed that the inhibition efficiency of 0. Read More

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Synthesis and in vivo screening of isosteviol derivatives as new cardioprotective agents.

Eur J Med Chem 2021 Mar 28;219:113396. Epub 2021 Mar 28.

School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, China. Electronic address:

Isosteviol, an ent-beyerane diterpenoid, has been repeatedly reported to possess potent cardioprotective activity. With the aim of discovering new cardioprotective derivatives from isosteviol, 47 compounds, including 40 new ones, were synthesized and evaluated in vivo using the easy-handling and efficient zebrafish model. The structure-activity relationship of this type of compounds was thus discussed. Read More

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The numerical probability of carcinogenicity to humans of some antimicrobials: Nitro-monoaromatics (including 5-nitroimidazoles), quinoxaline-1,4-dioxides (including carbadox), and chloramphenicol.

Toxicol In Vitro 2021 Apr 13:105172. Epub 2021 Apr 13.

Institute of Pharmaceutical Research, Faculty of Pharmacy, Universidad Central de Venezuela, Caracas, Venezuela.

Many substances are already tested in the long-term (2-year) rodent bioassay (RCB). Nonetheless, statements such as the following are common in the regulatory literature: "the significance of the carcinogenicity findings in rodents relative to the therapeutic use of drugs in humans is unknown." (U. Read More

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Antibacterial and Antifungal Polyketides from the Fungus PSU-MF16.

J Nat Prod 2021 Apr 16. Epub 2021 Apr 16.

Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ubon Ratchathani University, Ubon Ratchathani 34190, Thailand.

Seven new polyketides including a phenol (), two diphenyl ethers ( and ), two depsidones ( and ), and two phthalides ( and ) were isolated from the fungus PSU-MF16 along with 27 known compounds. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of and - were established using comparative analyses of calculated and experimental ECD spectra. Read More

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Synthesis of new urease enzyme inhibitors as antiulcer drug and computational study.

J Biomol Struct Dyn 2021 Apr 16:1-16. Epub 2021 Apr 16.

H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

In search of potent urease inhibitor indole analogues () were synthesized and evaluated for their urease inhibitory potential. All analogues () showed a variable degree of inhibitory interaction potential having IC value ranging between 0.60 ± 0. Read More

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Molecular optimization, docking, and dynamic simulation profiling of selective aromatic phytochemical ligands in blocking the SARS-CoV-2 S protein attachment to ACE2 receptor: an approach of targeted drug designing.

J Adv Vet Anim Res 2021 Mar 5;8(1):24-35. Epub 2021 Mar 5.

Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh.

Objectives: The comprehensive study aims to figure out the most effective aromatic phytochemical ligands among a number from a library, considering their pharmacokinetic efficacies in blocking "angiotensin-converting enzyme 2 (ACE2) receptor-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein" complex formation as part of a target-specific drug designing.

Materials And Methods: A library of 57 aromatic pharmacophore phytochemical ligands was prepared from where the top five ligands depending on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) and quantitative structure-activity relationship (QSAR)-based pharmacokinetic properties were considered. The selected ligands were optimized for commencing molecular docking and dynamic simulation as a complex with the ACE2 receptor to compare their blocking efficacy with the control drug. Read More

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Investigation of Covalent Warheads in the Design of 2-Aminopyrimidine-based FGFR4 Inhibitors.

ACS Med Chem Lett 2021 Apr 22;12(4):647-652. Epub 2021 Mar 22.

School of Pharmacy, Jinan University, #601 Huangpu Avenue West, Guangzhou 510632, China.

Covalent kinase inhibitors are rapidly emerging as a class of therapeutics with clinical benefits. Herein we report a series of selective 2-aminopyrimidine-based fibroblast growth factor receptor 4 (FGFR4) inhibitors exploring different types of cysteine-targeting warheads. The structure-activity relationship study revealed that the chemically tuned warheads α-fluoro acrylamide, vinylsulfonamide, and acetaldehyde amine were suitable as covalent warheads for the design of selective FGFR4 inhibitors. Read More

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Identification of Piperidine-3-carboxamide Derivatives Inducing Senescence-like Phenotype with Antimelanoma Activities.

ACS Med Chem Lett 2021 Apr 22;12(4):563-571. Epub 2021 Mar 22.

Medicinal Chemistry Group, Institut Pasteur Korea, 16 Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, South Korea.

This study evaluated the potential use of senescence-inducing small molecules in the treatment of melanoma. We screened commercially available small-molecule libraries with high-throughput screening and high-content screening image-based technology. Our findings showed an initial hit with the embedded -arylpiperidine-3-carboxamide scaffold-induced senescence-like phenotypic changes in human melanoma A375 cells without serious cytotoxicity against normal cells. Read More

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Preparation and characterization of curdlan with unique single-helical conformation and its assembly with Congo Red.

Carbohydr Polym 2021 Jul 26;263:117985. Epub 2021 Mar 26.

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071, PR China.

Elucidating the structure-activity relationship of curdlan is hampered by a lack of characterization with unique specific conformations (i.e., single- or triple-helix). Read More

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ERα-agonist and ERβ-antagonist bifunctional next-generation bisphenols with no halogens: BPAP, BPB, and BPZ.

Toxicol Lett 2021 Apr 12. Epub 2021 Apr 12.

Department of Chemistry, Faculty of Science, Kyushu University, Motooka 744, Nishi-ku, Fukuoka, 819-0395, Japan; Risk Science Research Institute, Ikimatsudai 3-7-5, Nishi-ku, Fukuoka, 819-0044, Japan. Electronic address:

As demonstrated for bisphenol AF (BPAF), the electrostatic halogen bond based on the London dispersion force of halogen atoms was found to be a major driving force of their bifunctional ERα-agonist and ERβ-antagonist activities. Because similar electronic effects are anticipated for hydrocarbon groups (alkyl or aryl groups), we hypothesized that bisphenol compounds consisting of such groups also work bifunctionally. In the present study, we examined bisphenol AP (BPAP), B (BPB), and Z (BPZ). Read More

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Comparative study on the structures of intra- and extra-cellular polysaccharides from Penicillium oxalicum and their inhibitory effects on galectins.

Int J Biol Macromol 2021 Apr 15;181:793-800. Epub 2021 Apr 15.

Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, China. Electronic address:

Here, we compare the content and composition of polysaccharides derived from the mycelium (40.4 kDa intracellular polysaccharide, IPS) and culture (27.2 kDa extracellular polysaccharide, EPS) of Penicillium oxalicum. Read More

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Designing QSARs for Parameters of High-Throughput Toxicokinetic Models Using Open-Source Descriptors.

Environ Sci Technol 2021 Apr 15. Epub 2021 Apr 15.

Office of Research and Development, Center for Computational Toxicology and Exposure, U.S. Environmental Protection Agency, 109 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709, United States.

The intrinsic metabolic clearance rate (Cl) and the fraction of the chemical unbound in plasma () serve as important parameters for high-throughput toxicokinetic (TK) models, but experimental data are limited for many chemicals. Open-source quantitative structure-activity relationship (QSAR) models for both parameters were developed to offer reliable predictions for a diverse set of chemicals regulated under the U.S. Read More

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Synthesis and structure-activity relationship study of novel 3-diethoxyphosphorylfuroquinoline-4,9-diones with potent antitumor efficacy.

Eur J Med Chem 2021 Apr 3;219:113429. Epub 2021 Apr 3.

Institute of Organic Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924, Łódź, Poland. Electronic address:

Herein we report an efficient synthesis of a series of regioisomeric N,O-syn and N,O-anti 3-diethoxyphosphorylfuroquinoline-4,9-diones combining furoquinoline-5,8-dione skeleton, present in several highly cytotoxic compounds, with diethoxyphosphoryl moiety. The cytotoxic activity of the obtained analogs was tested against two human cancer cell lines: promyelocytic leukemia HL-60 and breast cancer adenocarcinoma MCF-7 and for comparison on human umbilical vein endothelial cells HUVEC and mammary gland/breast MCF-10 A cells. Several diethoxyphosphorylfuroquinoline-4,9-diones proved to be highly cytotoxic for cancer cells with IC values even below 0. Read More

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Quantitative structure-activity relationship models for genotoxicity prediction based on combination evaluation strategies for toxicological alternative experiments.

Sci Rep 2021 Apr 13;11(1):8030. Epub 2021 Apr 13.

College of Medical Information Engineering, Guangdong Pharmaceutical University, Guangzhou, China.

Mutagenicity exerts adverse effects on humans. Conventional methods cannot simultaneously predict the toxicity of a large number of compounds. Most mutagenicity prediction models are based on a single experimental type and lack other experimental combination data as support, resulting in limited application scope and predictive ability. Read More

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Synthesis, α-glucosidase and α-amylase inhibitory activities, acute toxicity and molecular docking studies of thiazolidine-2,4-diones derivatives.

J Biomol Struct Dyn 2021 Apr 13:1-12. Epub 2021 Apr 13.

Laboratory of Pharmacology and Toxicology, Biopharmaceutical and Toxicological Analysis Research Team, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.

In the present study, a series of thiazolidine-2,4-diones derivatives () and () were synthesized and characterized by H NMR, C NMR and ESI-MS spectrometry. All compounds were screened for their α-glucosidase and α-amylase inhibitory activities. biological investigations revealed that most of compounds were active against α-glucosidase with IC values in the range of 43. Read More

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Design, Synthesis, and Antifungal Activity of Novel Longifolene-Derived Diacylhydrazine Compounds.

ACS Omega 2021 Apr 24;6(13):9104-9111. Epub 2021 Mar 24.

Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, Guangxi University for Nationalities, No. 188, Daxue Dong Road, Nanning, Guangxi 530006, China.

Succinate dehydrogenase (SDH) present in the inner mitochondrial membrane is an important target enzyme for the design of SDH inhibitor-type fungicides. Using SDH as the target enzyme, 22 novel longifolene-derived diacylhydrazine compounds were designed and synthesized using the renewable natural product longifolene as the starting material. Their structures were confirmed by IR, H NMR, C NMR, electrospray mass spectrometry, and elemental analysis. Read More

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The synthesis of furoquinolinedione and isoxazoloquinolinedione derivatives as selective Tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors.

Bioorg Chem 2021 Apr 1;111:104881. Epub 2021 Apr 1.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou 510006, China. Electronic address:

Based on our previous study on the development of the furoquinolinedione and isoxazoloquinolinedione TDP2 inhibitors, the further structure-activity relationship (SAR) was studied in this work. A series of furoquinolinedione and isoxazoloquinolinedione derivatives were synthesized and tested for enzyme inhibitions. Enzyme-based assays indicated that isoxazoloquinolinedione derivatives selectively showed high TDP2 inhibitory activity at sub-micromolar range, as well as furoquinolinedione derivatives at low micromolar range. Read More

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Radioligand and computational insight in structure - activity relationship of saccharin derivatives being ipsapirone and revospirone analogues.

Bioorg Med Chem Lett 2021 Apr 8:128028. Epub 2021 Apr 8.

Department of Medicinal Chemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland.

Schizophrenia and depression are diseases that significantly impede human functioning in society. Current antidepressant drugs are not fully effective. According to literature data, the effect on DR or 5-HTR can effectively reduce the symptoms of depression or schizophrenia. Read More

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Design and identification of a new farnesoid X receptor (FXR) partial agonist by computational structure-activity relationship analysis: Ligand-induced H8 helix fluctuation in the ligand-binding domain of FXR may lead to partial agonism.

Bioorg Med Chem Lett 2021 Apr 9;41:128026. Epub 2021 Apr 9.

Graduate School of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan; Faculty of Clinical Nutrition, Hiroshima International University, 5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan.

Farnesoid X receptor (FXR) controls gene-expression relevant to various diseases including nonalcoholic steatohepatitis and has become a drug target to regulate metabolic aberrations. However, some side effects of FXR agonists reported in clinical development such as an increase in blood cholesterol levels incentivize the development of partial agonists to minimize side effects. In this study, to identify a new partial agonist, we analyzed the computational structure-activity relationship (SAR) of FXR agonists previously developed in our laboratories using molecular dynamics simulations. Read More

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Exploring biologically active hybrid pharmacophore N-substituted hydrazine-carbothioamides for urease inhibition: In vitro and in silico approach.

Int J Biol Macromol 2021 Apr 9;182:534-544. Epub 2021 Apr 9.

Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan. Electronic address:

Urease is potential target for various human's health complications, such as peptic ulcer, gastric cancer and kidney stone formation. The present study was based on synthesis of new hybrid pharmacophore N-substituted hydrazine-carbothioamides as potential urease inhibitors. Presented method gave excellent yield in range of 85-95% for hydrazine-carbothioamides derivatives (3a-s) after reaction of mono- and disubstituted hydrazides (1a-k) and substituted isothiocyanates (2a-d). Read More

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The index of ideality of correlation improves the predictive potential of models of the antioxidant activity of tripeptides from frog skin (Litoria rubella).

Comput Biol Med 2021 Apr 3;133:104370. Epub 2021 Apr 3.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milano, Italy.

It is usually held that good-quality models for the biological activity of peptides must take into account their 3D architecture and descriptors of quantum mechanics. However, the present study shows that it is possible to build up models without these complex calculations. The structure of tripeptides represented by sequences of one-symbol abbreviations of the corresponding amino acids serves to build up quantitative structure-activity relationships for the antioxidant activity of tripeptides from frog skin. Read More

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