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

ORCID ID

0000-0002-0052-4926

Scopus Author ID

6506158277

Full item page

Scholarly Output

100

Articles

59

Citation Count

1305

Supervised Theses

26 Scholarly Output Search Results

Now showing 1 - 10 of 97

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
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.
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
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.
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
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.
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
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.
A Computational Study on the Amine-Oxidation Mechanism of Monoamine Oxidase: Insight Into the Polar Nucleophilic Mechanism
(Royal Soc Chemistry, 2006) Sağ Erdem, Safiye; Yelekçi, Kemal; Karahan, Özlem; Yıldız, İbrahim; Yelekçi, Kemal
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 of benzylamine increase the reaction rate. A good correlation between the log of the calculated rate constants and the electronic parameter (sigma) of the substituent was obtained. These results agree with the previous kinetic experiments on the effect of p-substituents on the reduction of MAO-A by benzylamine analogs. In addition the calculated rate constants showed a correlation with the rate of reduction of the flavin in MAO-A. In order to verify the results obtained from the PM3 method single-point B3LYP/6-31G*//PM3 calculations were performed. These results demonstrated a strong reduction in the activation energy for the reaction of benzylamine derivatives having electron-withdrawing substituents which is in agreement with the PM3 calculations and the previous experimental QSAR study. PM3 and B3LYP/6-31G* energy surfaces were obtained for the overall reaction of benzylamine with flavin. Results suggest that PM3 is a reasonable method for studying this kind of reaction. These theoretical findings support the proposed polar nucleophilic mechanism for MAO-A.
Targeting Cancer Epigenetic Modifiers: the Design of Isoform-Selective Histone Deacetylase Inhibitors
(Kadir Has Üniversitesi, 2018) Uba, Abdullahi İbrahim; Yelekçi, Kemal; Yelekçi, Kemal
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.
Homology Modeling of Human Histone Deacetylase 10 and Design of Potential Selective Inhibitors
(Taylor & Francis Inc, 2019) Uba, Abdullahi Ibrahim; Yelekçi, Kemal; Yelekçi, Kemal
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
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
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.
Novel 1,2,4-Triazoles Derived From Ibuprofen: Synthesis and in Vitro Evaluation of Their Mpges-1 Inhibitory and Antiproliferative Activity
(Springer, 2022) Bulbul, Bahadir; Yelekçi, Kemal; Ding, Kai; Çiftçi, Gamze; Zhan, Chang-Guo; Ciftci, Gamze; Yelekci, Kemal; Gurboga, Merve; Ozakpinar, Ozlem Bingol
Some novel triazole-bearing ketone and oxime derivatives were synthesized from Ibuprofen. 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 cervix cancer HeLa, and human chronic myelogenous leukemia K562 cell lines) were evaluated by MTT assay. In addition, mouse embryonic fibroblast cells (NIH/3T3) were also evaluated to determine the selectivity. Compounds 18, 36, and 45 were found to be the most cytotoxic, and their IC50 values were in the range of 17.46-68.76 mu M, against the tested cancer cells. According to the results, compounds 7 and 13 demonstrated good anti-inflammatory activity against the microsomal enzyme prostaglandin E2 synthase-1 (mPGES-1) enzyme at IC50 values of 13.6 and 4.95 mu M. The low cytotoxicity and non-mutagenity of these compounds were found interesting. Also, these compounds significantly prevented tube formation in angiogenesis studies. In conclusion, the anti-inflammatory and angiogenesis inhibitory activities of these compounds without toxicity suggested that they may be promising agents in anti-inflammatory treatment and they may be supportive agents for the cancer treatment. [GRAPHICS] .
In Silico Design of Novel and Highly Selective Cyclooxygenase-2 Inhibitors
(Kadir Has Üniversitesi, 2014) Mehmetoğlu, Tuğba; Yelekçi, Kemal; Yelekçi, Kemal
For many years, prevention of inflammation is achieved by inhibition of both cyclooxygenase (COX) enzymes; the eventual outcome is gastrointestinal toxicity. Selective inhibitor design for COX-2 initialized just after discovery of two distinct types of COX enzymes. Both isoforms of COX show great similarities at the active sites. It is still essential to find more potent, more selective and reversible COX-2 inhibitors. Crystallographic structures of COX-1 (pdb code: 1Q4G; Ovis aries COX-1 crystallized with Alpha-Methyl-4-Biphenylacetic, resolution 2.00 Å) and COX-2 (pdb code: 3NT1; Mus musculus COX-2 crystallized with naproxen, resolution 1.73 Å) isozymes have paved the way for computational modeling. In the present work, from receptor cavities of enzyme, suitable scaffolds for both isozyme are generated by using ZINCv12 fragment library. Accelrys 3.1's Discovery Studio Protocols and de novo design module were assigned in the derivation process of the scaffolds via link library to produce 1129 analogs. GOLD and AutoDock 4 are used to scan and define poses in catalytic sites of both COX isozymes. Known inhibitors were taken as a reference for verification of modeling studies. The best resultant inhibitors are subjected to ADMET test and validity is confirmed.