Browsing by Subject "Docking"
Now showing items 1-18 of 18
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Cis-cyclopropylamines as mechanism-based inhibitors of monoamine oxidases
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Publisher and Date:(Wiley-Blackwell, 2015)Cyclopropylamines inhibitors of monoamine oxidases (MAO) and lysine-specific demethylase (LSD1) provide a useful structural scaffold for the design of mechanism-based inhibitors for treatment of depression and cancer. For new compounds with the less common cis relationship and with an alkoxy substituent at the 2-position of the cyclopropyl ring the apparent affinity determined from docking experiments revealed little difference between the enantiomers. Using the racemate kinetic parameters for the ...
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The design of potent HIV-1 integrase inhibitors by a combined approach of structure-based virtual screening and molecular dynamics simulation
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Publisher and Date:(Taylor & Francis Ltd, 2018)Bu araştırmanın amacı, AIDS olarak bilinen insan bağışıklık sistemine etki eden, duraksamayan ve depresif bir hastalığa neden olan HIV-1'in tedavisi için potansiyel inhibitörleri elde etmektir. HIV-1 integraz inhibitörleri, HIV-1 enfeksiyonunun tedavisinde çok önemlidir. İntegraz enziminin (IN) inhibe edilmesi HIV-1 virüsünün çoğalma işleminin sonlandırılmasına neden olur. Böylece yaşam döngüsüne son verir. Bu inhibitörleri elde etmek için bilgisayar destekli in silico yaklaşım kullanılmıştır. ...
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Discovery of high affinity ligands for beta(2)-adrenergic receptor through pharmacophore-based high-throughput virtual screening and docking
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Publisher and Date:(Elsevier Science Inc, 2014)Novel high affinity compounds for human beta(2)-adrenergic receptor (beta(2)-AR) were searched among the clean drug-like subset of ZINC database consisting of 9928465 molecules that satisfy the Lipinski's rule of five. The screening protocol consisted of a high-throughput pharmacophore screening followed by an extensive amount of docking and rescoring. The pharmacophore model was composed of key features shared by all five inactive states of beta(2)-AR in complex with inverse agonists and antagonists. ...
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Docking studies on monoamine oxidase-B inhibitors: Estimation of inhibition constants (K-i) of a series of experimentally tested compounds
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Publisher and Date:(Pergamon-Elsevier Science Ltd, 2005)Monoamine oxidase (EC1.4.3.4
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Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies
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Publisher and Date:(Frontiers Media Sa, 2016)The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine ...
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In silico design of novel and highly selective cyclooxygenase-2 inhibitors
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Publisher and Date:(Kadir Has University, 2014)For many years, prevention of inflammation is achieved by inhibition of both cyclooxygenase (COX) enzymes; the eventual outcome is gastrointestinal toxicity. Selective inhibitor design for COX-2 initialized just after discovery of two distinct types of COX enzymes. Both isoforms of COX show great similarities at the active sites. It is still essential to find more potent, more selective and reversible COX-2 inhibitors. Crystallographic structures of COX-1 (pdb code: 1Q4G; Ovis aries COX-1 crystallized ...
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In silico design of selective monoamine Oxidase B inhibitors using indane ring
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Publisher and Date:(Kadir Has University, 2013)in the present work 209952 analogs of an indane scaffold were created using various fragment moieties at different position of indane ring. CHEMPLP module of GOLD program is utilized in the screening process. in order to obtain additional validation of selectivity and scoring values the first 100 best selective MAO inhibitor candidates are also tested via ChemScore and ASP scoring fuctions of Gold docking software AutoDock 4.2 and AutoDock Vina. inhibition constants and their poses in the active ...
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In silico design of selective neuronal nitric oxide synthase inhibitors in order to prevent neurodegenerative diseases
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Publisher and Date:(Kadir Has University, 2013)Nitric Oxide syntheses (NOS) are the family of enzymes which catalyzes the oxidation L-Arginine amino acid to nitric oxide molecule (NO) L-citrulline. Mammals contain three different NOS isozymes: Neuronal NOS (nNOS, in the brain), inducible NOS (iNOS, in macrophage cells), endothelial NOS (eNOS, the inner walls of blood vessels). Nitric Oxide (NO) is an important messenger molecule, which regulates several physiological functions in cardiovascular system and neuronal cells in the brain. Indeed, ...
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In silico identification of novel and selective monoamine oxidase B inhibitors
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Publisher and Date:(SPRINGER WIEN, 2013)Monoamine oxidases (MAO) A and B are flavin adenine dinucleotides containing enzymes bound to the mitochondrial outer membranes of the cells of the brain liver intestine and placenta as well as platelets. Recently selective MAO-B inhibitors have received increasing attention due to their neuroprotective properties and the multiple roles they can play in the therapy of neurodegenerative disorders. This study was based on 10 scaffolds that were selected from more than a million lead compounds in the ...
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In silico screening of neuronal nitric oxide synthase enzyme inhibitors
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Publisher and Date:(Kadir Has University, 2014)Three closely related isoforms of nitric oxide synthases (NOS) catalyze an important secondary messenger nitric oxide (NO) synthesis through oxidation of L-arginine to L-citrulline. These three NOS isoforms takes parts in different tissues for various physiological and pathological processes. Neuronal NOS (nNOS) produce NO in central and peripheral nervous system endothelial NOS (eNOS) plays role in endothelial cells and NO in macrophage cells is produced by inducible NOS (iNOS). Excessive NO ...
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In silico screening of tangible-potential inhibitor of methionine aminopeptidase 2 for the treatment of cancer
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Publisher and Date:(Kadir Has University, 2017)Methionine Aminopeptidases (MetAPs) are divalent-cofactor dependent enzymes that are responsible for cleaving the initiator Methionine from the newly synthesized polypeptides. These metalloproteases are classified into two distinct isoforms- MetAP1 and MetAP2. The MetAP2 isoform is upregulated in many cancerous cells. A selective inhibition of MetAP2 is an effective means of suppressing vascularization and limiting both the size and metastasis of solid tumors in a model organism. A selective and ...
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Insights into the binding mode of new N-substituted pyrazoline derivatives to MAO-A: docking and quantum chemical calculations
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Publisher and Date:(SPRINGER WIEN, 2013)The binding modes of four N-substituted pyrazoline derivatives as novel MAO-A inhibitory agents were investigated using docking and quantum chemical molecular modelling tools.
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New pyrazoline bearing 4(3H)-quinazolinone inhibitors of monoamine oxidase: Synthesis biological evaluation and structural determinants of MAO-A and MAO-B selectivity
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Publisher and Date:(Pergamon-Elsevier Science Ltd, 2009)A new series of pyrazoline derivatives were prepared starting from a quinazolinone ring and evaluated for antidepressant anxiogenic and MAO-A and -B inhibitory activities by in vivo and in vitro tests respectively. Most of the synthesized compounds showed high activity against both the MAO-A (compounds 4a-4h 4j-4n and 5g-5l) and the MAO-B (compounds 4i and 5a-5f) isoforms. However none of the novel compounds showed antidepressant activity except for 4b. The reason for such biological properties ...
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De novo selective inhibitor design to neuronal NOS enzyme and exploration of the binding site
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Publisher and Date:(Kadir Has University, 2013)Neural Nitric Oxide Synthase (nNOS) is an enzyme that plays a significant role in neural signal transmission among brain cells by carrying on Nitric Oxide(NO) generation. nNOS is one of the member of Nitric Oxide Synthase (NOS) enzyme family and has three isoforms; nNOS, eNOS and iNOS. Since NO is a highly reactive compound, NOS isozymes have many distinct functionalities on neural, endothelial and immune systems respectively. Despite these functionalities, their binding sites show great similarities ...
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Potential inhibitors of methionine aminopeptidase type II identified via structure-based pharmacophore modeling
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Publisher and Date:(Springer Science and Business Media Deutschland GmbH, 2021)Methionine aminopeptidase (MetAP2) is a metal-containing enzyme that removes initiator methionine from the N-terminus of a newly synthesized protein. Inhibition of the enzyme is crucial in diminishing cancer growth and metastasis. Fumagillin—a natural irreversible inhibitor of MetAP2—and its derivatives are used as potent MetAP2 inhibitors. However, because of their adverse effects, none of them has progressed to clinical studies. In search for potential reversible inhibitors, we built structure-based ...
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Synthesis and molecular modeling of some novel hexahydroindazole derivatives as potent monoamine oxidase inhibitors
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Publisher and Date:(Pergamon-Elsevier Science Ltd, 2009)A novel series of 2-thiocarbamoyl-234567-hexahydro-1H-indazole and 2-substituted thiocarbamoyl-33a 4567-hexahydro-2H-indazoles derivatives were synthesized and investigated for the ability to inhibit the activity of the A and B isoforms of monoamine oxidase (MAO). The target molecules were identified on the basis of satisfactory analytical and spectra data (IR H-1 NMR C-13 NMR D-2 NMR DEPT EI-MASS techniques and elemental analysis). Synthesized compounds showed high activity against both the MAO-A ...
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Synthesis and screening of hMAO inhibitory activities of some new 2-pyrazoline and hydrazone derivatives
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Publisher and Date:(Wiley-Blackwell, 2014)
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Synthesis Molecular Docking and Anticancer Activity of Diflunisal Derivatives as Cyclooxygenase Enzyme Inhibitors
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Publisher and Date:(MDPI, 2018)Cyclooxygenase enzymes play a vital role in inflammatory pathways in the human body. Apart from their relation with inflammation the additional involvement of COX-2 enzyme with cancer activity was recently discovered. In some cancer types the level of COX-2 enzyme is increased indicating that this enzyme could be a suitable target for cancer therapy. Based on these findings we have synthesized some new diflunisal thiosemicarbazides and 124-triazoles and tested them against androgen-independent ...
