14,982 results match your criteria inhibitors crystal


Screening of phytoconstituents as GSK-3β inhibitor and its implication in neuroblastoma: molecular docking, molecular dynamics, MM-PBSA binding energy, and in-vitro study.

J Biomol Struct Dyn 2021 Sep 27:1-14. Epub 2021 Sep 27.

Department of Natural Products, National Institute of Pharmaceutical Education and Research, Kolkata, India.

Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, primary regulator of various cellular activities varying from glycogen metabolism to cell proliferation and regulation. GSK-3β is associated with the pathogenesis of numerous human diseases, including cancer, metabolic disorder, and Alzheimer's disease. In this study, compounds were selected and further screened on the BOILED-Egg model. Read More

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September 2021

Structural studies provide new insights into the role of lysine acetylation on substrate recognition by CARM1 and inform the design of potent peptidomimetic inhibitors.

Chembiochem 2021 Sep 27. Epub 2021 Sep 27.

Leiden University Institute of Biology Leiden: Universiteit Leiden Instituut Biologie Leiden, Biological Chemistry Group, Leiden, NETHERLANDS.

The dynamic interplay of post-translational modifications (PTMs) in chromatin provides a communication system for the regulation of gene expression. An increasing number of studies have highlighted the role that such crosstalk between PTMs plays in chromatin recognition. In this study, (bio)chemical and structural approaches were applied to specifically probe the impact of acetylation of Lys 18 in the histone H3 tail peptide on peptide recognition by the protein methyltransferase CARM1. Read More

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September 2021

Structural basis for juvenile hormone biosynthesis by the juvenile hormone acid methyltransferase.

J Biol Chem 2021 Sep 22:101234. Epub 2021 Sep 22.

State Key Laboratory of Silkworm Genome Biology, Biological Science Research Center, Southwest University, Chongqing 400715, China; Chongqing Key Laboratory of Sericultural Science, Chongqing engineering and technology research center for novel silk materials, Southwest University, Chongqing 400715, China. Electronic address:

Juvenile hormone (JH) acid methyltransferase (JHAMT) is a rate-limiting enzyme that converts JH acids or inactive precursors of JHs to active JHs at the final step of JH biosynthesis in insects, and thus presents an excellent target for the development of insect growth regulators or insecticides. However, the three-dimensional properties and catalytic mechanism of this enzyme are not known. Herein, we report the crystal structure of the JHAMT apoenzyme, the three-dimensional holoprotein in binary complex with its cofactor S-adenosyl-L-homocysteine, and the ternary complex with S-adenosyl-L-homocysteine and its substrate methyl farnesoate. Read More

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September 2021

Structural dissection of sequence recognition and catalytic mechanism of human LINE-1 endonuclease.

Nucleic Acids Res 2021 Sep 23. Epub 2021 Sep 23.

Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.

Long interspersed nuclear element-1 (L1) is an autonomous non-LTR retrotransposon comprising ∼20% of the human genome. L1 self-propagation causes genomic instability and is strongly associated with aging, cancer and other diseases. The endonuclease domain of L1's ORFp2 protein (L1-EN) initiates de novo L1 integration by nicking the consensus sequence 5'-TTTTT/AA-3'. Read More

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September 2021

Discovery and evaluation of entry inhibitors for SARS-CoV-2 and its emerging variants.

J Virol 2021 Sep 22:JVI0143721. Epub 2021 Sep 22.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68131, USA.

The outbreak of SARS-CoV-2 is responsible for the COVID-19 pandemic. Despite unprecedented research and developmental efforts, SARS-CoV-2-specific antivirals are still unavailable for the treatment of COVID-19. In most instances, SARS-CoV-2 infection initiates with the binding of spike glycoprotein to the host cell ACE2 receptor. Read More

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September 2021

Exploration of the structural requirements of Aurora Kinase B inhibitors by a combined QSAR, modelling and molecular simulation approach.

Sci Rep 2021 Sep 21;11(1):18707. Epub 2021 Sep 21.

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.

Aurora kinase B plays an important role in the cell cycle to orchestrate the mitotic process. The amplification and overexpression of this kinase have been implicated in several human malignancies. Therefore, Aurora kinase B is a potential drug target for anticancer therapies. Read More

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September 2021

Advancing insights on β -cyclodextrin inclusion complexes with SSRIs through lens of X-ray diffraction and DFT calculation.

Authors:
Thammarat Aree

Int J Pharm 2021 Sep 17:121113. Epub 2021 Sep 17.

Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address:

Depression-the global crisis hastened by the coronavirus outbreak, can be efficaciously treated by the selective serotonin reuptake inhibitors (SSRIs). Cyclodextrin (CD) inclusion complexation is a method of choice for reducing side effects and improving bioavailability of drugs. Here, we investigate in-depth the β -CD encapsulation of sertraline (STL) HCl (1) and fluoxetine (FXT) HCl (2) by single-crystal X-ray diffraction and DFT complete-geometry optimization, in comparison to the reported complex of paroxetine (PXT) base. Read More

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September 2021

Synthesis, Fungicidal Activity, and Mechanism of Action of Pyrazole Amide and Ester Derivatives Based on Natural Products l-Serine and Waltherione Alkaloids.

J Agric Food Chem 2021 Sep 20. Epub 2021 Sep 20.

College of Agriculture, Liaocheng University, Liaocheng 252000, P. R. China.

The development of new green fungicides based on the structural optimization of natural products can effectively solve the problems of low safety and high pathogen resistance of traditional fungicides. In this paper, based on pyrazole amide compound with excellent fungicidal activity discovered in the previous work, a series of l-serine-derived pyrazole amide and waltherione alkaloid-derived pyrazole ester derivatives were synthesized. The structures were successively identified by H NMR, C NMR, high-resolution mass spectrometry, and X-ray single-crystal diffraction. Read More

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September 2021

Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors.

Front Mol Biosci 2021 1;8:718941. Epub 2021 Sep 1.

Department Genomics and Proteomics, Instituto de Biomedicina de Valencia, Spanish National Research Council (CSIC), Valencia, Spain.

Ribosome biogenesis is an emerging therapeutic target. It has been proposed that cancer cells are addicted to ribosome production which is therefore considered a druggable pathway in cancer therapy. Cancer cells have been shown to be more sensitive to inhibition of the ribosome production than healthy cells. Read More

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September 2021

Crystal Structure of Elongation Factor G1.

Front Mol Biosci 2021 3;8:667638. Epub 2021 Sep 3.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, And Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

() caused an estimated 10 million cases of tuberculosis and 1.2 million deaths in 2019 globally. The increasing emergence of multidrug-resistant and extensively drug-resistant is becoming a public health threat worldwide and makes the identification of anti- drug targets urgent. Read More

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September 2021

Discovery of highly potent human glutaminyl cyclase (QC) inhibitors as anti-Alzheimer's agents by the combination of pharmacophore-based and structure-based design.

Eur J Med Chem 2021 Sep 8;226:113819. Epub 2021 Sep 8.

Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

The inhibition of glutaminyl cyclase (QC) may provide a promising strategy for the treatment of early Alzheimer's disease (AD) by reducing the amount of the toxic pyroform of β-amyloid (Aβ) in the brains of AD patients. In this work, we identified potent QC inhibitors with subnanomolar IC values that were up to 290-fold higher than that of PQ912, which is currently being tested in Phase II clinical trials. Among the tested compounds, the cyclopentylmethyl derivative (214) exhibited the most potent in vitro activity (IC = 0. Read More

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September 2021

Indole Chloropyridinyl Ester-Derived SARS-CoV-2 3CLpro Inhibitors: Enzyme Inhibition, Antiviral Efficacy, Structure-Activity Relationship, and X-ray Structural Studies.

J Med Chem 2021 Sep 16. Epub 2021 Sep 16.

Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, United States.

Here, we report the synthesis, structure-activity relationship studies, enzyme inhibition, antiviral activity, and X-ray crystallographic studies of 5-chloropyridinyl indole carboxylate derivatives as a potent class of SARS-CoV-2 chymotrypsin-like protease inhibitors. Compound exhibited a SARS-CoV-2 3CLpro inhibitory IC value of 250 nM and an antiviral EC value of 2.8 μM in VeroE6 cells. Read More

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September 2021

Antiviral evaluation of hydroxyethylamine analogs: Inhibitors of SARS-CoV-2 main protease (3CLpro), a virtual screening and simulation approach.

Bioorg Med Chem 2021 Sep 4;47:116393. Epub 2021 Sep 4.

Department of Infectious Diseases, Mayo Clinic, Jacksonville, FL, USA. Electronic address:

The continued toll of COVID-19 has halted the smooth functioning of civilization on a global scale. With a limited understanding of all the essential components of viral machinery and the lack of structural information of this new virus, initial drug discovery efforts had limited success. The availability of high-resolution crystal structures of functionally essential SARS-CoV-2 proteins, including 3CLpro, supports the development of target-specific therapeutics. Read More

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September 2021

Phosphopantetheinyl transferase binding and inhibition by amidino-urea and hydroxypyrimidinethione compounds.

Sci Rep 2021 Sep 10;11(1):18042. Epub 2021 Sep 10.

Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31077, Toulouse, France.

Owing to their role in activating enzymes essential for bacterial viability and pathogenicity, phosphopantetheinyl transferases represent novel and attractive drug targets. In this work, we examined the inhibitory effect of the aminido-urea 8918 compound against the phosphopantetheinyl transferases PptAb from Mycobacterium abscessus and PcpS from Pseudomonas aeruginosa, two pathogenic bacteria associated with cystic fibrosis and bronchiectasis, respectively. Compound 8918 exhibits inhibitory activity against PptAb but displays no activity against PcpS in vitro, while no antimicrobial activity against Mycobacterium abscessus or Pseudomonas aeruginosa could be detected. Read More

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September 2021

Structural basis of O-methylation of (2-heptyl-)1-hydroxyquinolin-4(1H)-one and related compounds by the heterocyclic toxin methyltransferase Rv0560c of Mycobacterium tuberculosis.

J Struct Biol 2021 Sep 20;213(4):107794. Epub 2021 Sep 20.

Institute of Molecular Microbiology and Biotechnology, University of Münster, Münster, Germany. Electronic address:

The S-adenosyl-L-methionine-dependent methyltransferase Rv0560c of Mycobacterium tuberculosis belongs to an orthologous group of heterocyclic toxin methyltransferases (Htm) which likely contribute to resistance of mycobacteria towards antimicrobial natural compounds as well as drugs. Htm catalyzes the methylation of the Pseudomonas aeruginosa toxin 2-heptyl-1-hydroxyquinolin-4(1H)-one (also known as 2-heptyl-4-hydroxyquinoline N-oxide), a potent inhibitor of respiratory electron transfer, its 1-hydroxyquinolin-4(1H)-one core (QNO), structurally related (iso)quinolones, and some mycobactericidal compounds. In this study, crystal structures of Htm in complex with S-adenosyl-L-homocysteine (SAH) and the methyl-accepting substrates QNO or 4-hydroxyisoquinoline-1(2H)-one, or the methylated product 1-methoxyquinolin-4(1H)-one, were determined at < 1. Read More

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September 2021

Response surface modeling integrated microtiter plate assay for biofilm quantification.

Biofouling 2021 Sep 9:1-14. Epub 2021 Sep 9.

Department of Biotechnology & Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan (H.P.), India.

In this study, the effects of agitation, temperature, and pH on biofilm formation by were studied and quantified through response surface modeling. The microtiter plate assay was optimized to achieve conditions favoring maximum mycobacterial biofilm quantification. Optical density (OD) measurement using a crystal violet assay was performed to estimate the amount of biofilm formed. Read More

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September 2021

A Structure Based Study of Selective Inhibition of Factor IXa over Factor Xa.

Molecules 2021 Sep 3;26(17). Epub 2021 Sep 3.

Department of Physics, Pukyong National University, Busan 48513, Korea.

Blood coagulation is an essential physiological process for hemostasis; however, abnormal coagulation can lead to various potentially fatal disorders, generally known as thromboembolic disorders, which are a major cause of mortality in the modern world. Recently, the FDA has approved several anticoagulant drugs for Factor Xa (FXa) which work via the common pathway of the coagulation cascade. A main side effect of these drugs is the potential risk for bleeding in patients. Read More

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September 2021

Structural Insights and Docking Analysis of Adamantane-Linked 1,2,4-Triazole Derivatives as Potential 11β-HSD1 Inhibitors.

Molecules 2021 Sep 2;26(17). Epub 2021 Sep 2.

Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.

The solid-state structural analysis and docking studies of three adamantane-linked 1,2,4-triazole derivatives are presented. Crystal structure analyses revealed that compound crystallizes in the triclinic -1 space group, while compounds and crystallize in the same monoclinic 2/ space group. Since the only difference between them is the substitution on the aryl group, the electronic nature of these NO and halogen groups seems to have no influence over the formation of the solid. Read More

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September 2021

Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way, but It Is Still a Long Way Down.

Molecules 2021 Aug 27;26(17). Epub 2021 Aug 27.

Kaust Catalysis Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.

Mammalian cell surfaces are modified with complex arrays of glycans that play major roles in health and disease. Abnormal glycosylation is a hallmark of cancer; terminal sialic acid and fucose in particular have high levels in tumor cells, with positive implications for malignancy. Increased sialylation and fucosylation are due to the upregulation of a set of sialyltransferases (STs) and fucosyltransferases (FUTs), which are potential drug targets in cancer. Read More

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In silico evaluation of COVID-19 main protease interactions with honeybee natural products for discovery of high potential antiviral compounds.

Nat Prod Res 2021 Sep 9:1-7. Epub 2021 Sep 9.

Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

This research investigates antiviral potential of extracted honeybee products against COVID-19 main protease (Mpro) by computational methods. The crystal structure of COVID-19 Mpro was obtained from the protein data bank. Six synthetic drugs with antiviral properties were used as control samples in order to compare the results with those of natural ligands. Read More

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September 2021

Crystal structure of Aspergillus fumigatus AroH, an aromatic amino acid aminotransferase.

Proteins 2021 Sep 8. Epub 2021 Sep 8.

Department of Biochemical Sciences, Sapienza University of Rome, Rome.

Aspergillus fumigatus is a saprophytic ubiquitous fungus whose spores can trigger reactions such as allergic bronchopulmonary aspergillosis or the fatal invasive pulmonary aspergillosis. To survive in the lungs, the fungus must adapt to a hypoxic and nutritionally restrictive environment, exploiting the limited availability of aromatic amino acids (AAAs) in the best possible way, as mammals do not synthesize them. A key enzyme for AAAs catabolism in A. Read More

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September 2021

Structure-Based Optimization of Small Molecule Human Galactokinase Inhibitors.

J Med Chem 2021 Sep 7;64(18):13551-13571. Epub 2021 Sep 7.

National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.

Classic galactosemia is a rare disease caused by inherited deficiency of galactose-1 phosphate uridylyltransferase (GALT). Accumulation of galactose-1 phosphate (gal-1P) is thought to be the major cause of the chronic complications associated with this disease, which currently has no treatment. Inhibiting galactokinase (GALK1), the enzyme that generates galactose-1 phosphate, has been proposed as a novel strategy for treating classic galactosemia. Read More

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September 2021

Physicochemical tools for studying virus interactions with targeted cell membranes in a molecular and spatiotemporally resolved context.

Anal Bioanal Chem 2021 Sep 7. Epub 2021 Sep 7.

Department of Infectious Diseases, Sahlgrenska Academy at the University of Gothenburg, 413 46, Gothenburg, Sweden.

The objective of this critical review is to provide an overview of how emerging bioanalytical techniques are expanding our understanding of the complex physicochemical nature of virus interactions with host cell surfaces. Herein, selected model viruses representing both non-enveloped (simian virus 40 and human norovirus) and enveloped (influenza A virus, human herpes simplex virus, and human immunodeficiency virus type 1) viruses are highlighted. The technologies covered utilize a wide range of cell membrane mimics, from supported lipid bilayers (SLBs) containing a single purified host membrane component to SLBs derived from the plasma membrane of a target cell, which can be compared with live-cell experiments to better understand the role of individual interaction pairs in virus attachment and entry. Read More

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September 2021

Antibacterial and anti-biofilm activities of histidine kinase YycG inhibitors against Streptococcus agalactiae.

J Antibiot (Tokyo) 2021 Sep 6. Epub 2021 Sep 6.

Department of Infectious Diseases and the Key Lab of Endogenous Infection, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China.

This study aims to investigate the antibacterial and anti-biofilm activities of YycG inhibitors H2-60 and H2-81 against Streptococcus agalactiae. A total of 118 nonduplicate S. agalactiae clinical isolates were collected, and the minimal inhibitory concentrations (MICs) of H2-60 and H2-81 were determined. Read More

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September 2021

Conformational dynamics linked to domain closure and substrate binding explain the ERAP1 allosteric regulation mechanism.

Nat Commun 2021 Sep 6;12(1):5302. Epub 2021 Sep 6.

Department of Pathology, University of Massachusetts Medical School, Worcester, MA, USA.

The endoplasmic-reticulum aminopeptidase ERAP1 processes antigenic peptides for loading on MHC-I proteins and recognition by CD8 T cells as they survey the body for infection and malignancy. Crystal structures have revealed ERAP1 in either open or closed conformations, but whether these occur in solution and are involved in catalysis is not clear. Here, we assess ERAP1 conformational states in solution in the presence of substrates, allosteric activators, and inhibitors by small-angle X-ray scattering. Read More

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September 2021

FMS-like tyrosine kinase-3 (FLT3) inhibitors with better binding affinity and ADMET properties than sorafenib and gilteritinib against acute myeloid leukemia: in silico studies.

J Biomol Struct Dyn 2021 Sep 6:1-12. Epub 2021 Sep 6.

Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, Saudia Arabia.

Over 30-35% of patients down with AML are caused by mutations of FLT3-ITD and FLT3-TKD which keeps the protein activated while it activates other signaling proteins downstream that are involved in cell proliferation, differentiation, and survival. As drug targets, many inhibitors are already in clinical practice. Unfortunately, the average overall survival rate for patients on medication suffering from AML is 5 years despite the huge efforts in this field. Read More

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September 2021

Synergistic Antibacterial and Antibiofilm Activity of the MreB Inhibitor A22 Hydrochloride in Combination with Conventional Antibiotics against and Clinical Isolates.

Int J Microbiol 2021 25;2021:3057754. Epub 2021 Aug 25.

Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.

In the era of antibiotic resistance, the bacterial cytoskeletal protein MreB is presented as a potential target for the development of novel antimicrobials. Combined treatments of clinical antibiotics with anti-MreB compounds may be promising candidates in combating the resistance crisis, but also in preserving the potency of many conventional drugs. This study aimed to evaluate the synergistic antibacterial and antibiofilm activities of the MreB inhibitor A22 hydrochloride in combination with various antibiotics. Read More

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Synthesis of erythrodiol C-ring derivatives and their activity against Chlamydia trachomatis.

Steroids 2021 Sep 1;175:108912. Epub 2021 Sep 1.

Faculty of Pharmacy, "Victor Babes" University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, Timisoara 300041, Romania.

To develop new potential agents against Chlamydia trachomatis among oleanane type triterpenoids the synthesis, spectral and X-ray analysis as well as antimicrobial screening of C-12 oxygen and nitrogen derivatives of erythrodiol is presented. The reduction of methyl 3β-acetoxy-12-oxo-oleanoate with LiAlH led to isomeric erythrodiol 12β- and 12α-hydroxy-derivatives, their stereochemistry with respect to the position of hydroxyl-group at C-12 was determined based on the multiplets splitting patterns, the magnitude of the spin-spin interaction, and NOESY interactions. Methyl 3β-acetoxy-12-oxo-oleanoate was transformed to 12E-hydroxyimino- and 12E-methoxyimino-derivatives by the interaction with NHOH∙HCl or CHONH∙HCl, respectively. Read More

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September 2021

Talaromyoxaones A and B: Unusual Oxaphenalenone Spirolactones as Phosphatase Inhibitors from the Marine-Derived Fungus SCSIO 41517.

J Org Chem 2021 Sep 3;86(18):12831-12839. Epub 2021 Sep 3.

CAS Key Laboratory of Tropical Marine Bioresources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.

(+)- and (-)-talaromyoxaones A and B ( and , respectively), two new oxaphenalenone derivatives with a hemiacetal frame and an unprecedented spirolactone frame of a 2',3,4'-spiro[isobenzofuran-1,3'-pyran]-3-one unit that show biosynthetic enantiodivergence, and two new oxaphenalenone analogues (±)-11-apopyrenulin () and (+)- or (-)-abeopyrenulin () were isolated from the marine-derived fungus SCSIO 41517. Their structures were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations of ECD spectra. Compounds and showed selective inhibitory activity against phosphatases SHP1, SHP2, and MEG2 with IC values of 1. Read More

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September 2021

Design, Synthesis, Biological Evaluation, and Molecular Modeling of Novel 4-Chromene Analogs as Potential Succinate Dehydrogenase Inhibitors.

J Agric Food Chem 2021 Sep 3;69(36):10709-10721. Epub 2021 Sep 3.

School of Science, Xihua University, Chengdu 610039, P.R. China.

Thirty-one new 4-chromene derivatives were designed and synthesized. Their structures were identified with IR, H NMR, C NMR, and HRMS. The crystal structure of compound was determined by single-crystal X-ray diffraction. Read More

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September 2021