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 97

Citation - WoS: 12
Citation - Scopus: 9
Homology Modeling Andin Silicodesign of Novel and Potential Dual-Acting Inhibitors of Human Histone Deacetylases Hdac5 and Hdac9 Isozymes
(2020) Elmezayen, Ammar D.; Yelekçi, Kemal; Yelekçi, Kemal; Molecular Biology and Genetics
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 study, we constructed human HDAC5 and HDAC9 protein models using human HDAC4 (PDB:2VQM_A) as a template by the means of homology modeling approach. Based on the Z-score of the built models, model M0014 of HDAC5 and model M0020 of HDAC9 were selected. The models were verified by MODELLER and validated using the Web-based PROCHECK server. All selected known inhibitors displayed reasonable binding modes and equivalent predicted Ki values in comparison to the experimental binding affinities (Ki/IC50). The known inhibitor Rac26 showed the best binding affinity for HDAC5, while TMP269 showed the best binding affinity for HDAC9. The best two compounds, CHEMBL2114980 and CHEMBL217223, had relatively similar inhibition constants against HDAC5 and HDAC9. The built models and their complexes were subjected to molecular dynamic simulations (MD) for 100 ns. Examining the MD simulation results of all studied structures, including the RMSD, RMSF, radius of gyration and potential energy suggested the stability and reliability of the built models. Accordingly, the results obtained in this study could be used for designing de novo inhibitors against HDAC5 and HDAC9. Communicated by Ramaswamy H. Sarma
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 - WoS: 0
Epitope Based Hla Matching by Using Antibody Reactivity With High Resolution Allele Typing and Hlamatchmaker Algorithm Based Software
(Wiley, 2017) Karadeniz, Sedat Tanju; Yelekçi, Kemal; Akgül, Sebahat Usta; Çiftçi, Hayriye Şentürk; Öğret, Yeliz; Oğuz, Fatma; Yelekçi, Kemal; Aydın, Filiz; Molecular Biology and Genetics
[Abstract Not Available]
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: 27
Citation - Scopus: 31
Homology Modeling of Human Histone Deacetylase 10 and Design of Potential Selective Inhibitors
(Taylor & Francis Inc, 2019) Uba, Abdullahi Ibrahim; Yelekçi, Kemal; Yelekçi, Kemal; Molecular Biology and Genetics
Histone deacetylases (HDACs) are implicated in the pathology of various cancers, and their pharmacological blockade has proven to be promising in reversing the malignant phenotypes. However, lack of crystal structures of some of the human HDAC isoforms (e.g., HDAC10) hinders the design of the isoform-selective inhibitor. Here, the recently solved X-ray crystal structure of Danio rerio (zebrafish) HDAC10 (Protein Data Bank (PDB) ID; 5TD7, released on 24 May 2017) was retrieved from the PDB and used as a template structure to model the three-dimensional structure of human HDAC10. The overall quality of the best model (M0017) was assessed by computing its z-score-a measure of the deviation of the total energy of the structure with respect to an energy distribution derived from random conformations and by docking of known HDAC10 inhibitors to its catalytic cavity. Furthermore, to identify potential HDAC10-selective inhibitor ligand-based virtual screening was carried out against the ZINC database. The free modeled structure of HDAC10 and its complexes with quisinostat and the highest-ranked compound ZINC19749069 were submitted to molecular dynamics simulation. The comparative analysis of root-mean-squared deviation, root-mean-squared fluctuation, radius of gyration (Rg), and potential energy of these systems showed that HDAC10-ZINC19749069 complex remained the most stable over time. Thus, M0017 could be potentially used for structure-based inhibitor against HDAC10, and ZINC19749069 may provide a scaffold for further optimization. Communicated by Ramaswamy H. Sarma
Citation - WoS: 6
Citation - Scopus: 8
The Design of Potent Hiv-1 Integrase Inhibitors by a Combined Approach of Structure-Based Virtual Screening and Molecular Dynamics Simulation
(Taylor & Francis Ltd, 2018) Samorlu, Augustine S.; Yelekçi, Kemal; Yelekçi, Kemal; Uba, Abdullahi Ibrahim; Molecular Biology and Genetics
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. Temelde, Otava Kimya Kütüphanesi tarandı ve inhibitör tasarımında kullanılan sistematik yaklaşımlar uygulandı, böylece dört güçlü integraz inhibitörü bulundu. İnhibitörlerin enzime bağlanma değerleri PyRx ve AutoDock 4.2 doklama programları kullanılarak gerçekleştirildi. Çalışmada bir kimyasalın güçlü bir inhibitör olabilmesi için hesaplanan serbest bağ enerjisi = -8.00 kcal / mol veya daha az olması ve integrazın aktif bölgesinde bulunan 3 önemli amino asidinden herhangi biri ile de etkileşimde bulunması kriterine uyulmuştur. Discovery Studio Visualizer, inhibitörlerin yapısını çizmekte, inhibitörü komplekslerinin resimlerini üretmekte, enzim ve inhibitör arasındaki etkileşimin türünü belirlememizi sağlayan 2D ve 3D yapıları görüntülemek için kullanıldı. Elde edilen dört güçlü inhibitörden, kendimizin tasarladığı moleküllerden (Ki= 652.83 nanomolar bir ve bağlanma serbest enerjisi -8.44kcal / mol), kalan üç inhibitörde, Otava Kimya Kütüphanesi'nde tarandı ve Otava koduyla parantez içerisinde listelenmiştir. Bunların inhibisyon sabiti ve bağlanma enerjileri sırasıyla; 107320240, Ki=131.7nm, -9.39kcal/ mol; 109750115, Ki= 44.19nm, -10.03kcal / mol; 111150115 Ki = 395.19nm, -8.74kcal / mol olarak bulunmuştur.