Browsing by Author "Demir, Ayhan S."

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Citation - WoS: 2
Citation - Scopus: 3
Aryl Butenoic Acid Derivatives as a New Class of Histone Deacetylase Inhibitors: Synthesis in Vitro Evaluation and Molecular Docking Studies
(Scientific Technical Research Council Turkey-Tubitak, 2014) Esiyok, Peruze Ayhan; Yelekçi, Kemal; Seven, özlem; Eymur, Guluzar; Tatar, Gamze Bora; Erden, Didem Dayangaç; Yelekçi, Kemal; Yurter, Hayat; Demir, Ayhan S.
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.
Citation - WoS: 0
Comp 297-Experimental and Molecular Docking Simulation Studies of Histone Deacetylases (hdacs) Enzyme Inhibitors
(Amer Chemical Soc, 2007) Yelekçi, Kemal; Yelekçi, Kemal; Bora, Gamze; Dayangaç-Erden, Didem; Ayhan, Peruze; Dalkara, Sevim; Demir, Ayhan S.; Erdem-Yurter, Hayat
[Abstract Not Available]
Citation - WoS: 46
Citation - Scopus: 46
Histone Deacetylase Inhibition Activity and Molecular Docking of (e )-Resveratrol: Its Therapeutic Potential in Spinal Muscular Atrophy
(Wiley, 2009) Dayangac-Erden, Didem; Yelekçi, Kemal; Bora, Gamze; Ayhan, Peruze; Kocaefe, Çetin; Dalkara, Sevim; Yelekçi, Kemal; Demir, Ayhan S.; Erdem-Yurter, Hayat
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. Among our candidate prodrug library we found that (E )-resveratrol which is one of the polyphenolic compounds inhibited histone deacetylase activity in a concentration-dependent manner and half-maximum inhibition was observed at 650 mu m. Molecular docking studies showed that (E )-resveratrol had more favorable free energy of binding (-9.09 kcal/mol) and inhibition constant values (0.219 mu m) than known inhibitors. To evaluate the effect of (E )-resveratrol on SMN2 expression spinal muscular atrophy type I fibroblast cell lines was treated with (E )-resveratrol. The level of full-length SMN2 mRNA and protein showed 1.2- to 1.3-fold increase after treatment with 100 mu m (E )-resveratrol in only one cell line. These results indicate that response to (E )-resveratrol treatment is variable among cell lines. This data demonstrate a novel activity of (E )-resveratrol and that it could be a promising candidate for the treatment of spinal muscular atrophy.
Homology Modeling and Normal Mode Analysis of Human Nr1-Nr2a Nmda Type Receptors
(Kadir Has Üniversitesi, 2017) Demir, Ayhan S.; Eşsiz, Şebnem; Gökhan Eşsiz, Şebnem
N-Methyl-D-Aspartate (NMDA) receptors are ionotropic glutamate receptors located in the membrane of the nerve cells. The normal receptor activity has a vital importance in consciousness and normal brain functions. Neuronal death occurs as a result of overstimulation of NMDA-type glutamate receptors and leads to diseases such as stroke epilepsy Alzheimer's and Parkinson's. There are two recently available x-ray structures one from Xenopus laevis and the other one from Rattus norvegicus. First the structures were analyzed and compared especially for ion channel parts by considering the general problems that arise when crystallizing structures of membrane proteins. Then human GluNR1-GluNR2A type NMDA receptor structure was modeled by homology modeling based on the Xenopus laevis template. NMDA receptor structure is a large membrane protein complex thus we followed a couple of different strategies such as modeling by the individual monomer modeling as a tetramer and modeling as a tetramer without loops then adding loops with loop modeling. Final models were chosen according to the model assessment scoring function. Subsequently elastic network analysis was used to understand the dynamics of the structural variations which govern the function of the protein. 20 slowest modes of NMDA receptor were examined according to 8 parameters which are found to be functionally important in previous NMDA studies. The 3th slowest mode was noticeable regarding to gating mechanism. in Mode 3 a twist motion of the TMD part rotates clockwise parallel to the membrane while LBD and TMD together rotate counter-clock wise parts cause opening of the channel. Mode 3 showed the relationship between TMD girdles LDB and M3-TMD linker. Similarly Mode 9 like Mode 3 showed the same relationship. in addition Mode 9 showed like a breathing motion or expansion motion along the channel axis. We hope that these modes will be tested by a more through all atom molecular dynamics study of apo and ligand bound human NMDA structure in the near future.
Citation - WoS: 0
Medi 333-Histone Deacetylase Inhibition Activity of Resveratrol and Its Analogs
(Amer Chemical Soc, 2007) Dayangac-Erden, Didem; Yelekçi, Kemal; Ayhan, Peruze; Bora, Gamze; Yelekçi, Kemal; Dalkara, Sevim; Demir, Ayhan S.; Erdem-Yurter, Hayat
[Abstract Not Available]
Citation - WoS: 150
Citation - Scopus: 166
Molecular Modifications on Carboxylic Acid Derivatives as Potent Histone Deacetylase Inhibitors: Activity and Docking Studies
(Pergamon-Elsevier Science Ltd, 2009) Bora-Tatar, Gamze; Yelekçi, Kemal; Dayangac-Erden, Didem; Demir, Ayhan S.; Dalkara, Sevim; Yelekçi, Kemal; Erdem-Yurter, Hayat
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 of inhibitor-enzyme complexes. Of these compounds caffeic acid derivatives such as chlorogenic acid and curcumin were found to be highly potent compared to sodium butyrate which is a well-known HDAC inhibitor. (C) 2009 Elsevier Ltd. All rights reserved.