Kemal Yelekçi

Yelekçi, Kemal

Name Variants

Kemal Y.
KEMAL YELEKÇI
Yelekci K.
Y., Kemal
Yelekçi, Kemal
Yelekci, Kemal
Yelekçi K.
Y.,Kemal
Yelekçi, KEMAL
Yelekçi,K.
Kemal YELEKÇI
YELEKÇI, Kemal
Yelekci,Kemal
Kemal, Yelekci
K. Yelekçi
YELEKÇI, KEMAL
Yelekçi, K.
Kemal Yelekçi
Yelekci,K.
Kemal, Yelekçi
Yelekçi, Kemal
Yelekçi, Kemal

Job Title

Prof. Dr.

Email Address

yelekci@khas.edu.tr

Main Affiliation

Molecular Biology and Genetics

Sustainable Development Goals Report Points

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Scholarly Output

100

Articles

59

Citation Count

1305

Supervised Theses

26 Scholarly Output Search Results

Now showing 1 - 10 of 67

In Silico Screening of Potent Histon Demethylase1 (lsd1) Enzyme Inhibitor
(Kadir Has Üniversitesi, 2020) TAHER AL-RIKABI, MARYAM MUHSIN; Yelekçi, Kemal; Yelekçi, Kemal; Molecular Biology and Genetics
Histone lysine specific demethylase (LSD1) is one of the main enzymes which regulates histone demethylation which in return regulates different epigenetic processes such DNA replication and transcription also gene silencing. Moreover, recent studies have made a direct yet unclear link between LSD1 and the development of several diseases such viral infections, neurodegenerative diseases and most commonly cancer. An overexpression of the enzyme has been observed in different types of cancer including; acute myeloid leukemia (AML), breast cancer, lung cancer and prostate cancer. This observation led to the development of two LSD1 inhibitors; Tranylcypromine and 2-[4-methoxy-phenyl] Cyclopropylamine yet both have demonstrated low selectivity against the enzyme therefore this study along with many others solo focus on finding more potent LSD1 inhibitors through applying newly developed computer aided drug design (in silico) approaches. In this study Zinc15 database was screened in order to obtain pre-synthesized potential lead compounds. 40 thousand compounds were obtained, prepared and docked in two phases, firstly with PyRx autodock vina software and afterwards the compounds that have passed the first evaluation were further docked in autodock4 software and a total of 24 compounds have shown potential with a binding energy of -8.00 kcal/mol and less. Later on, Discovery Studio Visualizer software was used to generate 2D and 3D diagram pictures of the enzyme – ligand complex to further display and investigate the ligand interactions in the enzymes binding pocket.
Citation - Scopus: 1
Investigation of Synthesis, Molecular Modelling and Monoaminoxidase Inhibitor Activity of a New 2-Pyrazoline Compound
(Refik Saydam National Public Health Agency (RSNPHA), 2018) Evranos-Aksöz, B.; Yelekçi, Kemal; Uçar, G.; Yelekçi, K.; Molecular Biology and Genetics
Objective: Isoforms of monoamine oxidase (MAO-A and -B) which are responsible for the degradation of neuromediators are involved in many diseases, and MAO inhibitors are used for the treatment of some diseases such as depression, Alzheimer's and Parkinson's diseases. Thus, a novel compound, SH2U was synthesized and its ability for the inhibition of human MAO (hMAO) activity was investigated by our group. In addition, the interaction of SH2U with hMAO isoforms have been investigated in detail using molecular modelling technics. It has been found that SH2U inhibited hMAO-B potently, selectively, competitively and reversibly suggesting that the novel compound may be a promising drug agent for the treatment of Parkinson's and Alzheimer's diseases. Methods: 1-(3,5-dichloro-2-hydroxyphenyl)-3- p-tolylprop-2-ene-1-on (3',5'-Dichloro-2'-hydroxy- 4-methyl chalcone) was prepared via the reaction of p-tolualdehyde and 3',5'-Dichloro-2'-hydroxy acetophenone in methanol in the presence of KOH. Then, the obtained chalcone was treated with isonicotinic acid hydrazide under reflux in ethanol to give (3-(3,5-Dichloro-2-hydroxy phenyl)-5-p-tolyl- 4,5-dihydropyrazol-1-yl) (pyridin-4-yl) methanone. The interaction of SH2U with hMAO isoforms was investigated fluorometrically using commercial kits. The interaction between SH2U and hMAO was also analyzed using AutoDock 4.2.6 program. Results: The structure of compound SH2U was confirmed using IR, Mass, 1 H-NMR and elemental analysis methods. SH2U appeared as a potent, selective, reversible and nontoxic hMAO-B inhibitor. Mode of inhibition was found to be competitive. Interactions of the new compound with the active site of hMAO-B were clarified using molecular modelling studies. Conclusion: Compound SH2U inhibited hMAO-B potently, selectively, competitively and reversibly. The synthesized compound is found to be more potent and selective than selegiline, the known irreversible MAO-B inhibitor, indicating that SH2U appears as a promising active molecule to be used in the treatment of Parkinson's and Alzheimer's diseases. © 2018 Refik Saydam National Public Health Agency (RSNPHA).Amaç: Nöromediatörlerin yikimindan sorumlu olan monoamin oksidaz (MAO) enziminin izoformlarinin (MAO-A ve -B) birçok hastalik ile yakindan ilişkili olduğu; MAO inhibitörlerinin depresyon, Parkinson ve Alzheimer hastaliği gibi hastaliklarin tedavisinde kullanildigi bilinmektedir. Grubumuzca daha etkin, tersinir ve az yan etkili yeni bir MAO inhibitörü (SH2U bileşiği) sentezlenmiş ve bu bileşiğin insan MAO enzimini (hMAO) inhibe etme yeteneği incelenmiştir. Ayrica bu yeni bileşiğin hMAO ile etkileşimi, moleküler modelleme çalişmalari ile detayli bir şekilde araştirilmiştir. Sentezlenen yeni bileşiğin hMAO'yu kuvvetli bir şekilde yarişmali ve tersinir olarak inhibe ettiği bulunmuştur. Söz konusu bileşiğin Parkinson ve Alzheimer hastaliklarinin tedavisinde ümit verici bir ilaç etken maddesi olabileceği düşünülmektedir. Yöntem: 3',5'-Dikloro-2'-hidroksi asetofenon ile p-tolualdehit'in metanol içinde KOH varliginda reaksiyona girmesiyle 1-(3,5-dikloro-2-hidroksifenil)- 3-p-tolil prop-2-en-1-on (3',5'-Dikloro-2'-hidroksi-4- metil şalkon) bileşiği sentez edilmiştir. Daha sonra elde edilen bu bileşiğin etanol içerisinde geri çeviren sogutucu altinda izonikotinik asit hidrazit ile muamele edilmesiyle [3-(3,5-dikloro-2-hidroksifenil)-5-p-tolil-4,5- dihidropirazol-1-il] (piridin-4-il) metanon bileşiği sentez edilmiştir. Yapisi doğrulanan bu bileşiğin hMAO enzimi ile etkileşimi, ticari tayin kiti kullanilarak fluorometrik bir yöntemle incelenmiştir. Ayrica, söz konusu yeni bileşik ile hMAO arasindaki etkileşimler, moleküler modelleme çalişmalari ile aydinlatilmiştir. Bulgular: Sentezlenen bileşiğin yapisi, IR, Mass, 1H-NMR ve elemental analiz yöntemleri kullanilarak doğrulanmiştir. Yapisi doğrulanan bu bilesigin etkin, seçici, tersinir, toksik olmayan bir hMAO-B inhibitörü olduğu ve inhibisyonun yarişmali olduğu görülmüştür. Moleküler yerleştirme programi kullanilarak bileşiğin hMAO-B enziminin aktif bölgesinde hangi amino asit yan zincirleri ile ne tür girişimleri yaptiği belirlenmiştir. Sonuç: Yeni sentezlenen SH2U bileşiği, hMAO-B enzimini kuvvetle, seçici, yarişmali ve tersinir olarak inhibe etmistir. Sentezledigimiz bilesik, bilinen seçici ama tersinmez MAO-B inhibitörü olan selejilin'den daha etkin ve seçici, tersinir olarak hMAO-B enzimini inhibe etmiştir ve Parkinson ile Alzheimer hastaliği tedavisinde kullanilabilecek bir ilaç etken maddesi olarak ümit vadetmektedir. © 2018 Refik Saydam National Public Health Agency (RSNPHA).
Citation - WoS: 0
Citation - Scopus: 0
Design, Synthesis, Molecular Modeling, and Bioactivity Evaluation of 1,10-Phenanthroline and Prodigiosin (ps) Derivatives and Their Copper(i) Complexes Against Mtor and Hdac Enzymes as Highly Potent and Effective New Anticancer Therapeutic Drugs
(Frontiers Media Sa, 2022) Cetin, M. Mustafa; Yelekçi, Kemal; Peng, Wenjing; Unruh, Daniel; Mayer, Michael F.; Mechref, Yehia; Yelekci, Kemal; Molecular Biology and Genetics
Breast cancer is the second type of cancer with a high probability of brain metastasis and has always been one of the main problems of breast cancer research due to the lack of effective treatment methods. Demand for developing an effective drug against breast cancer brain metastasis and finding molecular mechanisms that play a role in effective treatment are gradually increasing. However, there is no effective anticancer therapeutic drug or treatment method specific to breast cancer, in particular, for patients with a high risk of brain metastases. It is known that mTOR and HDAC enzymes play essential roles in the development of breast cancer brain metastasis. Therefore, it is vital to develop some new drugs and conduct studies toward the inhibition of these enzymes that might be a possible solution to treat breast cancer brain metastasis. In this study, a series of 1,10-phenanthroline and Prodigiosin derivatives consisting of their copper(I) complexes have been synthesized and characterized. Their biological activities were tested in vitro on six different cell lines (including the normal cell line). To obtain additional parallel validations of the experimental data, some in silico modeling studies were carried out with mTOR and HDAC1 enzymes, which are very crucial drug targets, to discover novel and potent drugs for breast cancer and related brain metastases disease.
Citation - WoS: 11
Citation - Scopus: 20
Evaluation of Selective Human Mao Inhibitory Activities of Some Novel Pyrazoline Derivatives
(SPRINGER WIEN, 2013) Salgin-Goksen, Umut; Yelekçi, Kemal; Yabanoglu-Ciftci, Samiye; Ercan, Ayse; Yelekçi, Kemal; Ucar, Gulberk; Gokhan-Kelekçi, Nesrin; Molecular Biology and Genetics
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 moclobemide and selegiline and all the compounds were found to inhibit human MAO-A selectively. The inhibition profile was found to be competitive and reversible for all compounds by in vitro tests. Among the compounds examined compounds 5ae 5af and 5ag were more selective than moclobemide with respect to the K (i) values experimentally found. In addition the compound 5bg showed MAO-A inhibitor activity as well as moclobemide. A series of experimentally tested compounds (5ae-5ch) were docked computationally to the active site of the MAO-A and MAO-B isoenzyme. The AUTODOCK 4.01 program was employed to perform automated molecular docking.
Citation - WoS: 4
Citation - Scopus: 5
Synthesis and evaluation of antiproliferative and mPGES-1 inhibitory activities of novel carvacrol-triazole conjugates
(Acg Publications, 2022) Yelekçi, Kemal; Kulabas, Necla; Guerboga, Merve; oezakpinar, Oezlem Bingoel; ciftci, Gamze; Yelekci, Kemal; Liu, Jianyang; Molecular Biology and Genetics
Some novel triazole-bearing acetamide derivatives 9-26 were synthesized starting from carvacrol. All synthesized compounds were characterized by FTIR,1H-NMR,13C-NMR and MS data. In vitro cytotoxic activities of all synthesized molecules against five cancer lines (human breast cancer MCF-7, human lung cancer A549, human prostate cancer PC-3, human chronic myelogenous leukemia K562, human neuroblastoma SH-SY5Y cell lines) were evaluated by MTT assay. Compounds were also tested on mouse embryonic fibroblast cells (NIH/3T3) to determine selectivity. Eighteen target compounds 9-26 were screened for their mPGES-1 and COX-1/2 inhibitory activities. Of these compounds, 26 (KUC16D425) showed the highest mPGES-1 inhibition at 10 mu M. This compound has also been observed to induce apoptosis and inhibit cell migration in MCF-7 cells. In silico molecular docking calculations were performed to understand the binding interactions of compounds with target proteins. ADMET predictions were also done to evaluate drug-like properties of the novel compounds.
Targeting Cancer Epigenetic Modifiers: the Design of Isoform-Selective Histone Deacetylase Inhibitors
(Kadir Has Üniversitesi, 2018) Uba, Abdullahi İbrahim; Yelekçi, Kemal; Yelekçi, Kemal; Molecular Biology and Genetics
Epigenetic alterations are believed to be the common hallmark of human cancers. Histone deacetylase (HDAC) inhibitors have proven to be effective in cancer cases where HDACs are up-regulated. However lack of selectivity of many of the HDAC inhibitors in clinical use and those at various stages of preclinical and clinical trials causes toxicity to the normal cells. it is believed that the continuous identification of isoform-selective HDAC inhibitors can eliminate this adverse effect — a task that remains particularly challenging due to the high sequence and structural conservations around the active site of HDAC isoforms. The original contribution of this study was analyzing the similarity among class i HDACs (1 2 3 and 8) and class iib HDACs (6 and 10) by sequence and structural alignments catalytic channel extraction and identification of catalytically essential amino acid residues. in addition homology model of human HDAC10 was built using a recently-released X-ray crystal structure of Danio rerio (zebrafish) HDAC10 as a template. Using these data isoform-selective HDAC inhibitors were designed by topology-based scaffold hopping structure- and ligand-based virtual screening. The top inhibitors (in terms of both binding affinity and selectivity) were subjected to structure-based in silico absorption distribution metabolism elimination and toxicity (ADMET) prediction which showed their druglikeness. Furthermore their docking complexes were submitted to molecular dynamics (MD) simulations to examine the stability of ligand binding modes. These potential isoform-selective HDAC inhibitors showed stable binding mode over time of the simulation. They can therefore serve as drug candidates or viable lead compounds for further modeling-based and experimental optimization towards the design of safe potent and selective HDAC inhibitors.
Citation - WoS: 31
Citation - Scopus: 30
New 2-Pyrazoline and Hydrazone Derivatives as Potent and Selective Monoamine Oxidase A Inhibitors
(AMER CHEMICAL SOC, 2021-02) Salgın-Göksen, Umut; Yelekçi, Kemal; Telli, Gökçen; Erikci, Açelya; Dedecengiz, Ezgi; Tel, Banu Cahide; Kaynak, F. Betül; Yelekçi, Kemal; Ücar, Gülberk; Gökhan-Kelekçi, Nesrin; Molecular Biology and Genetics
Thirty compounds having 1-[2-(5-substituted-2-benzoxazolinone-3-yl) acetyl]-3,5-disubstitutedphenyl-2-pyrazoline structure and nine compounds having N'-(1,3-disubstitutedphenylallylidene)-2-(5-substituted- 2-benzoxazolinone-3-yl)-acetohydrazide skeleton were synthesized and evaluated as monoamine oxidase (MAO) inhibitors. All of the compounds exhibited selective MAO-A inhibitor activity in the nanomolar or low micromolar range. The results of the molecular docking for hydrazone derivatives supported the in vitro results. Five compounds, 6 (0.008 mu M, Selectivity Index (SI): 9.70 x 10(-4)), 7 (0.009 mu M, SI: 4.55 x 10(-5)), 14 (0.001 mu M, SI: 8.00 x 10(-4)), 21 (0.009 mu M, SI: 1.37 x 10(-5)), and 42 (0.010 mu M, SI: 5.40 x 10(-6)), exhibiting the highest inhibition and selectivity toward hMAO-A and nontoxic to hepatocytes were assessed for antidepressant activity as acute and subchronic in mice. All of these five compounds showed significant antidepressant activity with subchronic administration consistent with the increase in the brain serotonin levels and the compounds crossed the blood-brain barrier according to parallel artificial membrane permeation assay. Compounds 14, 21, and 42 exhibited an ex vivo MAO-A profile, which is highly consistent with the in vitro data.
Citation - WoS: 17
Citation - Scopus: 20
In Silico Design of Novel and Highly Selective Lysine-Specific Histone Demethylase Inhibitors
(Scientific Technical Research Council Turkey-Tubitak, 2011) Akdoğan, Ebru Demet; Akdoğan, Ebru Demet; Erman, Burak; Yelekçi, Kemal; Yelekçi, Kemal; Molecular Biology and Genetics
Histone lysine-specific demethylase (LSD1) is involved in a wide range of epigenetic processes and plays important roles in gene silencing DNA transcription DNA replication DNA repair and heterochromatin formation. Its active site shows a resemblance to those of 2 homologous enzymes monamine oxidase A and B (MAO-A and MAO-B.) In the present work starting from suitable scaffolds and generating thousands of structures from them 10 potential inhibitors were obtained with structural and physicochemical properties selectively suitable for inhibiting LSD1. iLib Diverse software was used to generate the diverse structures and 3 docking tools CDOCKER GOLD and AutoDock were used to find the most probable potential inhibitor based on its binding affinity. The dispositions of the candidate molecules within the organism were checked by ADMET_PSA_2D (polar surface area) versus ADMET_AlogP98 (the logarithm of the partition coefficient between n-octanol and water) and their suitability is discussed. The LSD1 inhibition activities of the candidates were compared with the properties of trans-2-phenylcyclopropylamine (tranylcypromine) and 2-(4-methoxy-phenyl) cyclopropylamine which are the 2 known inhibitors of LSD1.
In Silico Identification of Physiological Substrates and Inhibitors of Serum Paraoxonase 1 Enzyme
(Kadir Has Üniversitesi, 2014) Karabıyık, Talha; Yelekçi, Kemal; Yelekçi, Kemal; Molecular Biology and Genetics
Paraoxonase 1 (PON1) as an important antioxidant enzyme against oxidative stress has been implicated in the pathogenesis of a number of disorders including cancer cardiovascular and several other diseases. Although there has been considerable progress in understanding the PON1 enzyme its precise physiological substrate and function still remain inconclusive. Discovery of new PON1 substrates or inhibitors will provide better understanding of PON1’s cardiovascular protective and antioxidant effects. PON1 is known to show lactonase aryl esterase and phosphotriesterase (paraoxonase) activity. PON1 having two calcium ions within its central tunnel shows six-bladed ?-propeller with each arm comprising of four ?-sheets. The structural Ca2+ is buried whereas the catalytic Ca2+ lies at the bottom of the activesite cavity. in this study metabolites of Human Metabolome Database (HMDB) version 3.0 containing over 40000 metabolites were docked against the PON1 structure (PDB iD: 3SRE) determined by Ben-David et al. in a virtual screening scenario using AutoDock 4.2 and metabolites were evaluated in terms of docking energy and docking pose. The best 2000 metabolites in terms of docking energy were inspected one by one and 97 of them were selected due to their chemical groups that the PON1 may work on. These 97 metabolites were further evaluated in terms of their docking poses and this further evaluation revealed that 10 out of 97 had the correct docking pose. These aforementioned metabolites are sorgolactone indoxyl sulfate 5- methoxyhinokinin enterolactone (-)-arctigenin epoxybergamottin pandamarilactone 32 (-)-matairesinol alectrol isoalantolactone. Except indoxyl sulfate all of them are of plant origin. it is known that PON1 activity is negatively correlated with high intake of vegetables. With this data and docking energies of metabolites of plant origin mentioned above in hand it is suggested that these metabolites of plant origin may be PON1 inhibitors. indoxyl sulfate plays roles in mechanisms of various diseases and causes oxidative stress. This metabolite also has considerably low docking energy and may also be a PON1 inhibitor. To be certain about the PON1 inhibitory potential of these mentioned 10 metabolites laboratory assays should be carried out. -- Abstract'tan.
Ekmek Mayası (saccharomyces Cerevisiae) Yardımı ile L-3,4- Dihitroksifenil Alanin (l-dopa) için Yeni Bir Sentez Yöntemi
(TUBITAK Scientific & Technical Research Council Turkey, 1997) Yelekçi, Kemal; Yelekçi, Kemal; Hamamcı, Haluk; Kahraman, M. Vezir; Karataş, Sevim; Molecular Biology and Genetics
Ekmek mayası (saccharomyces cerevisiae) kolay ve ucuz bulunan bir reaktif olmasına karşın, organik kimyada yaptığı tepkimeler hem ilginç hem de diğer sentez yöntemleri ile yapılması ya imkansız ya da çok zordur. Bu amaçla klasik organik sentez yöntemleri ve maya kullanılarak daha önce sentezi bu yolla denenmeyen, anti parkinson ilacı L-3,4-Dihidroksifenilalanin'in sentezine yönelik ikisi orjinal dört önemli substurat hazırlanacak ve bu substratlar üzerinde bulunan karbon karbon çift bağı ekmek mayası ile stereospesifık olarak indirgenmeye çalışılacaktır.