Browsing by Subject "Molecular docking"
Now showing items 1-18 of 18
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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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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:(Tübitak, 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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Assessing protein-ligand binding modes with computational tools: the case of PDE4B
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Publisher and Date:(Springer, 2017)In a first step in the discovery of novel potent inhibitor structures for the PDE4B family with limited side effects we present a protocol to rank newly designed molecules through the estimation of their IC values. Our protocol is based on reproducing the linear relationship between the logarithm of experimental IC values [(IC)] and their calculated binding free energies (). From 13 known PDE4B inhibitors we show here that (1) binding free energies obtained after a docking process by AutoDock are ...
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Carboxylic acid derivatives display potential selectivity for human histone deacetylase 6: Structure-based virtual screening molecular docking and dynamics simulation studies
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Publisher and Date:(Elsevier Science, 2018)Human histone deacetylase 6 (HDAC6) has been shown to play a major role in oncogenic cell transformation via deacetylation of alpha-tubulin making it a viable target of anticancer drug design and development. The crystal structure of HDAC6 catalytic domain 2 has been recently made available providing avenues for structure-based drug design campaign. Here in our continuous effort to identify potentially selective HDAC6 inhibitors structure-based virtual screening of similar to 72 461 compounds was ...
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Designing of multi-targeted molecules using combination of molecular screening and in silico drug cardiotoxicity prediction approaches
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Publisher and Date:(Elsevier Science Inc, 2014)We have previously investigated and reported a set of phenol- and indole-based derivatives at the binding pockets of carbonic anhydrase isoenzymes using in silico and in vitro analyses. In this study we extended our analysis to explore multi-targeted molecules from this set of compounds. Thus 26 ligands are screened at the binding sites of 229 proteins from 5 main enzyme family classes using molecular docking algorithms. Derived docking scores are compared with reported results of ligands at ...
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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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Exploration of the binding pocket of histone deacetylases: the design of potent and isoform-selective inhibitors
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Publisher and Date:(Tübitak, 2017)Histone deacetylases (HDACs) are enzymes that act on histone proteins to remove the acetyl group and thereby regulate the chromatin state. HDACs act not only on histone protein but also nonhistone proteins that are key players in cellular processes such as the cell cycle, signal transduction, apoptosis, and more. “Classical” HDACs have been shown to be promising targets for anticancer drug design and development. However, the selectivity of HDAC inhibitors for HDAC isoforms remains the motivation ...
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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 ...
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Identification of potential inhibitors of human methionine aminopeptidase (type II) for cancer therapy: Structure-based virtual screening, ADMET prediction and molecular dynamics studies
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Publisher and Date:(Elsevier, 2020)Methionine Aminopeptidases MetAPs are divalent-cofactor dependent enzymes that are responsible for the cleavage of the initiator Methionine from the nascent polypeptides. MetAPs are classified into two isoforms: namely, MetAP1 and MetAP2. Several studies have revealed that MetAP2 is upregulated in various cancers, and its inhibition has shown to suppress abnormal or excessive blood vessel formation and tumor growth in model organisms. Clinical studies show that the natural product fumagillin, and ...
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Molecular docking study based on pharmacophore modeling for novel PhosphodiesteraseIV ınhibitors
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Publisher and Date:(Wiley-VCH Verlag GmbH, 2012)In this study pharmacophore modelling was carried out for novel PhosphodiesteraseIV (PDEIV) inhibitors. A pharmacophore-based virtual screening which resulted in 1959 hit compounds was performed with six chemical databases. The pharmacophore screening was proven to be successful in discriminating active and inactive inhibitors using a set of compounds with known activity obtained from ChEMBL database. Furthermore the Lipinskis rule of five was applied for physicochemical filtering of the hit ...
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Molecular modifications on carboxylic acid derivatives as potent histone deacetylase inhibitors: Activity and docking studies
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Publisher and Date:(Pergamon-Elsevier Science Ltd, 2009)In the light of known HDAC inhibitors 33 carboxylic acid derivatives were tested to understand the structural requirements for HDAC inhibition activity. Several modifications were applied to develop the structure-activity relationships of carboxylic acid HDAC inhibitors. HDAC inhibition activities were investigated in vitro by using HeLa nuclear extract in a fluorimetric assay. Molecular docking was also carried out for the human HDAC8 enzyme in order to predict inhibition activity and the 3D poses ...
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New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies
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Publisher and Date:(Elsevier France-Editions Scientifiques Medicales Elsevier, 2017)Azole antifungals are potent inhibitors of fungal lanosterol 14 alpha demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design synthesis and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl) ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 mu g/mL against Candida albicans. Additionally ...
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Synthesis and Screening of Human Monoamine Oxidase-A Inhibitor Effect of New 2-Pyrazoline and Hydrazone Derivatives
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Publisher and Date:(Wiley-VCH Verlag GmbH, 2015)A group of 35-diaryl-2-pyrazoline and hydrazone derivatives was prepared via the reaction of various chalcones with hydrazide compounds in ethanol. Twenty original compounds were synthesized. Ten of these original compounds have a pyrazoline structure nine of these original compounds have a hydrazone structure and one of these original compounds has a chalcone structure. Structural elucidation of the compounds was performed by IR H-1 NMR C-13 NMR mass spectral data and elemental analyses. These ...
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Synthesis anticancer activity and molecular modeling of etodolac-thioether derivatives as potent methionine aminopeptidase (type II) inhibitors
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Publisher and Date:(Wiley, 2018)A series of (RS)-1-{[5-(substituted)sulfanyl-4-substituted-4H-124-triazole-3-yl]methyl}-18-diethyl-1349-tetrahydropyrano[34-b]indoles (5a-v) were designed and synthesized using a five-step synthetic protocol that involves substituted benzyl chlorides and (RS)-5-[(18-diethyl-1349-tetrahydropyrano[34-b]indole-1-yl)methyl]-4-substituted-24-dihydro-3H-124-triazole-3-thiones in the final step. The synthesized derivatives were evaluated for cytotoxicity and anticancer activity in vitro using the MTT ...
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Synthesis molecular modeling and in vitro screening of monoamine oxidase inhibitory activities of some novel hydrazone derivatives
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Publisher and Date:(SPRINGER WIEN, 2013)Thirteen 2-[2-(5-methyl-2-benzoxazolinone-3-yl)acetyl]-3/4/5-substituted benzylidenehydrazine derivatives were synthesized by reacting 2-(5-methyl-2-benzoxazolinone-3-yl)acetylhydrazine and substituted benzaldehydes in neutral and acid/base catalyzed conditions and a comparison was made in terms of their yields and reaction times. The structures of all compounds were confirmed by IR H-1 NMR C-13 NMR mass spectral data and elemental analyses. All the compounds were investigated for their ability ...
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Synthesis Molecular Modelling and Antibacterial Activity Against Helicobacter pylori of Novel Diflunisal Derivatives as Urease Enzyme Inhibitors
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Publisher and Date:(Bentham Science Publ Ltd, 2019)Background: The main factor for the prolongation of the ulcer treatment in the gastrointestinal system would be Helicobacter pylori infection which can possibly lead to gastrointestinal cancer. Triple therapy is the treatment of choice by today's standards. However observed resistance among the bacterial strains can make the situation even worse. Therefore there is a need to discover new targeted antibacterial therapy in order to make success in the eradication of H. pylori infections. Methods: ...
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Synthesis of some novel hydrazone and 2-pyrazoline derivatives: Monoamine oxidase inhibitory activities and docking studies
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Publisher and Date:(Pergamon-Elsevier Science Ltd, 2014)A novel series of 2-pyrazoline and hydrazone derivatives were synthesized and investigated for their human monoamine oxidase (hMAO) inhibitory activity. All compounds inhibited the hMAO isoforms (MAO-A or MAO-B) competitively and reversibly. With the exception of 5i which was a selective MAO-B inhibitor all derivatives inhibited hMAO-A potently and selectively. According to the experimental K-i values compounds 6e and 6h exhibited the highest inhibitory activity towards the hMAO-A whereas compound ...
