Browsing Araştırma Çıktıları / Scopus by KHAS Author "Yelekçi, Kemal"
Now showing items 1-20 of 47
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A computational study on the amine-oxidation mechanism of monoamine oxidase: Insight into the polar nucleophilic mechanism
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Publisher and Date:(Royal Soc Chemistry, 2006)The proposed polar nucleophilic mechanism of MAO was investigated using quantum chemical calculations employing the semi-empirical PM3 method. In order to mimic the reaction at the enzyme's active site the reactions between the flavin and the p-substituted benzylamine substrate analogs were modeled. Activation energies and rate constants of all the reactions were calculated and compared with the published experimental data. The results showed that electron-withdrawing groups at the para position ...
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Absolute configuration and biological profile of pyrazoline enantiomers as MAO inhibitory activity
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Publisher and Date:(Wiley, 2019)A new racemic pyrazoline derivative was synthesized and resolved to its enantiomers using analytic and semipreparative high-pressure liquid chromatography. The absolute configuration of both fractions was established using vibrational circular dichroism. The in vitro monoamine oxidase (MAO) inhibitory profiles were evaluated for the racemate and both enantiomers separately for the two isoforms of the enzyme. The racemic compound and both enantiomers were found to inhibit hMAO-A selectively and ...
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Aryl butenoic acid derivatives as a new class of histone deacetylase inhibitors: synthesis in vitro evaluation and molecular docking studies
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Publisher and Date:(Scientific Technical Research Council Turkey-Tubitak, 2014)New aryl butenoic acid derivatives have been synthesized by combining hydroxy- or methoxy-substituted phenyl rings as the capping group with a double bond in the short linker as well as metal binding groups enoic ester and salts bearing either methyl or morpholine. These compounds have been shown to possess promising histone deacetylase inhibition activities via in vitro fluorometric assay and molecular docking studies.
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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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Corrected Panel-Reactive Antibody Positivity Rates for Hypersensitized Patients in Turkish Population With Calculated Panel-Reactive Antibody Software
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Publisher and Date:(Elsevier Science Inc, 2017)Introduction. High rates of panel-reactive antibody (PRA) may decrease the chance of kidney transplantation and may result in long waiting periods before transplantation. The calculated PRA (cPRA) is performed based on unacceptable HLA antigens. These antigens are identified by a program that was created based on the antibodies that developed against the HLA antigens circulating in serum and on the risk of binding of these antibodies to antigens. The antigen profile of the population and antigen ...
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Crystallographic structure versus homology model: a case study of molecular dynamics simulation of human and zebrafish histone deacetylase 10
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Publisher and Date:(Taylor & Francis, 2020)Histone deacetylase (HDAC) 10 has been implicated in the pathology of various cancers and neurodegenerative disorders, making the discovery of novel inhibitors of the isoform an important endeavor. However, the unavailability of crystallographic structure of human HDAC10 (hHDAC10) hinders structure-based drug design effort. Previously, we reported the homology modeled structure of human HDAC10 built using the crystallographic structure of Danio rerio (zebrafish) HDAC10 (zHDAC10) (Protein Data Bank ...
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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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Design, Synthesis and hMAO Inhibitory Screening of Novel 2-Pyrazoline Analogues
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Publisher and Date:(Bentham Science Publ Ltd, 2017)Aim and Objective: MAO inhibitors have a significant effect on the nervous system since they act in regulation of neurotransmitter concentrations. Neurotransmitter levels are critical for a healthy nervous system. MAO inhibitors can be used in the treatment of neurological disorders such as depression, Parkinson's disease and Alzheimer's disease, as the increase or decrease of some neurotransmitter concentrations is associated with these neurological disorders. This study was conducted to discover ...
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Discovery of novel isoform-selective histone deacetylases 5 and 9 inhibitors through combined ligand-based pharmacophore modeling, molecular mocking, and molecular dynamics simulations for cancer treatment
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Publisher and Date:(Elsevier, 2021-07)Class IIa histone deacetylases (HDACs) 5 and 9 play crucial roles in several human disorders such as cancer, making them important targets for drug design. Continuous research is pursed to overcome the cytotoxicity side effect that comes with the currently available broad-spectrum HDACs inhibitors. Herein, common features of active HDACs inhibitors in clinical trials and use have been calculated to generate the best pharmacophore hypothesis. Guner-Henry scoring system was used to validate the ...
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Docking of novel reversible monoamine oxidase-B inhibitors: efficient prediction of ligand binding sites and estimation of inhibitors thermodynamic properties
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Publisher and Date:(Printed in The Netherlands, 2007)Monoamine oxidase (MAO, EC 1.4.3.4) is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known target for antidepressant, Parkinson's disease and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened ...
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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:(Front. Neurosci, 2016)HIGHLIGHTS Many CNS targets are being explored for multi-target drug designNew databases and cheminformatic methods enable prediction of primary pharmaceutical target and off-targets of compoundsQSAR, virtual screening and docking methods increase the potential of rational drug design 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 ...
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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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Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes
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Publisher and Date:(TAYLOR & FRANCIS LTD, 2020)In December 2019, COVID-19 epidemic was described in Wuhan, China, and the infection has spread widely affecting hundreds of thousands. Herein, an effort was made to identify commercially available drugs in order to repurpose them against coronavirus by the means of structure-based virtual screening. In addition, ZINC15 library was used to identify novel leads against main proteases. Human TMPRSS2 3D structure was first generated using homology modeling approach. Our molecular docking study showed ...
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Evaluation of selective human MAO inhibitory activities of some novel pyrazoline derivatives
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Publisher and Date:(SPRINGER WIEN, 2013)A series of 1-[2-((5-methyl/chloro)-2-benzoxazolinone-3-yl)acetyl]-35-diaryl-45-dihydro-1H-pyrazole derivatives were prepared by reacting 2-((5-methyl/chloro)-2-benzoxazolinone-3-yl)acetylhydrazine with appropriate chalcones. The chemical structures of all compounds were confirmed by elemental analyses IR H-1 NMR and ESI-MS. All the compounds were investigated for their ability to selectively inhibit monoamine oxidase (MAO) by in vitro tests. MAO activities of the compounds were compared with ...
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Examining the stability of binding modes of the co-crystallized inhibitors of human HDAC8 by molecular dynamics simulation
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Publisher and Date:(Taylor & Francis Inc, 2019)Histone deacetylase (HDAC) 8 has been implicated as a potential therapeutic target in a variety of cancers neurodegenerative disorders metabolic dysregulation and autoimmune and inflammatory diseases. Several nonselective HDAC inhibitors have been co-crystallized with HDAC8. Molecular dynamics (MD) studies may yield valuable information on the structural stabilities of the complexes over time as determined by various pharmacophore features of the co-crystallized inhibitors. Here using 11 unmodified ...
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Flavonoids from Sideritis Species: Human Monoamine Oxidase (hMAO) Inhibitory Activities Molecular Docking Studies and Crystal Structure of Xanthomicrol
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Publisher and Date:(MDPI, 2015)The inhibitory effects of flavonoids on monoamine oxidases (MAOs) have attracted great interest since alterations in monoaminergic transmission are reported to be related to neurodegenerative diseases such as Parkinson's and Alzheimer's diseases and psychiatric disorders such as depression and anxiety thus MAOs may be considered as targets for the treatment of these multi-factorial diseases. In the present study four Sideritis flavonoids xanthomicrol (1) isoscutellarein 7-O-[6'''-O-acetyl--d-all ...
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Histone Deacetylase Inhibition Activity and Molecular Docking of (E )-Resveratrol: Its Therapeutic Potential in Spinal Muscular Atrophy
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Publisher and Date:(Wiley, 2009)Spinal muscular atrophy is an autosomal recessive motor neuron disease that is caused by mutation of the survival motor neuron gene (SMN1) but all patients retain a nearly identical copy SMN2. The disease severity correlates inversely with increased SMN2 copy. Currently the most promising therapeutic strategy for spinal muscular atrophy is induction of SMN2 gene expression by histone deacetylase inhibitors. Polyphenols are known for protection against oxidative stress and degenerative diseases. ...
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Homology modeling andin silicodesign of novel and potential dual-acting inhibitors of human histone deacetylases HDAC5 and HDAC9 isozymes
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Publisher and Date:(2020)Histone deacetylases (HDACs) are a group of enzymes that have prominent and crucial effect on various biological systems, mainly by their suppressive effect on transcription. Searching for inhibitors targeting their respective isoforms without affecting other targets is greatly needed. Some histone deacetylases have no crystal structures, such as HDAC5 and HDAC9. Lacking proper and suitable crystal structure is obstructing the designing of appropriate isoform selective inhibitors. Here in this ...
