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.

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

99

Articles

58

Citation Count

1305

Supervised Theses

26 Scholarly Output Search Results

Now showing 1 - 10 of 91

In silico design of novel and highly selective cyclooxygenase-2 inhibitors
(Kadir Has Üniversitesi, 2014) 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.
Docking study of resveratrol like molecules on histone deacetylase
(Kadir Has Üniversitesi, 2016) Yelekçi, Kemal; Yelekçi, Kemal
The modulation of histone acetylation plays a pivotal role in the regulation of gene expression by governing the state of lysine residues located on the amino – terminal tails of histone proteins. A dynamic balance of histone acetylation /deacetylation is maintained by histone acetyl transferases(HAT) and histone deacetylases(HDACs) . Due to their fundamental role in gene expression HDAC family have been associated with basic cellular events and disease states such as cell growth differentiation and cancer information. in particular distinct class i and ii are overexpressed in some cancer disease. HDAC inhibitors structurally can be grouped into hydroxamates cyclic peptides aliphatic acids benzamine’s. HDAC inhibitors (HDACi) and histone acetyl transferase activators increase histone acetylation. HDAC8 is a class i HDAC implicated as a therapeutic target for a various disease including disorder cell growth. The structure of this enzyme reaveled unique features as its conformational flexibility. The architecture of the catalytic site and the channel rim of HDAC8 adapt to accommodate various ligands according to their size shape and chemical properties. Ýn this study the native TSA ligand of HDAC8 (code 1T64) re docked to observe the inhibition constant (Ki) with different parameter such as rotatable bonds and X Y Z coordinates. From this approach starting de nova design from resveratrol compound that is suggested to play a role in the preventation of some disease such as inhibition of tumour initiation. The resveratrol scaffold was used to create 100 hundred analogues by substituting chemical groups to observe the changes in the binding energy and inhibition constant by molecular docking using Autodock4.2. These 100 analogues were evaluated in terms of the inhibition constant (Ki) and 20 of them selected due to their lowest inhibition constant (Ki) and binding energy. The fact that HDAC8 is a promising target for cancer therapy these molecules can be potential anticancer agents if additional laboratory assays are carried out to ascertain their inhibitory effects.
Citation Count: 3
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.
Citation Count: 51
Drug Design for CNS Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3D-QSAR and Virtual Screening Methodologies
(Frontiers Media Sa, 2016) Yelekçi, Kemal; Mavridis, Lazaros; Djikic, Teodora; Vucicevic, Jelica; Agbaba, Danica; Yelekçi, Kemal; Mitchell, John B. O.
The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug discovery programs. A probabilistic method, the ParzenRosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands targeting AChE/MAO-A/MAO-B and also D-1-R/D-2-R/5-HT2A-R/H-3-R are promising novel drug candidates with improved efficacy and beneficial neuroleptic and procognitive activities in treatment of Alzheimer's and related neurodegenerative diseases. Structural information for drug targets permits docking and virtual screening and exploration of the molecular determinants of binding, hence facilitating the design of multi-targeted drugs. The crystal structures and models of enzymes of the monoaminergic and cholinergic systems have been used to investigate the structural origins of target selectivity and to identify molecular determinants, in order to design MTDLs.
Citation Count: 4
Computational Chemistry and Molecular Modeling of Reversible MAO Inhibitors
(Humana Press Inc., 2023) Yelekçi, Kemal; Erdem, S.S.
Proper elucidation of drug-target interaction is one of the most significant steps at the early stages of the drug development research. Computer-aided drug design tools have substantial contribution to this stage. In this chapter, we specifically concentrate on the computational methods widely used to develop reversible inhibitors for monoamine oxidase (MAO) isozymes. In this context, current computational techniques in identifying the best drug candidates showing high potency are discussed. The protocols of structure-based drug design methodologies, namely, molecular docking, in silico screening, and molecular dynamics simulations, are presented. Employing case studies of safinamide binding to MAO B, we demonstrate how to use AutoDock 4.2.6 and NAMD software packages. © 2023, The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.
Citation Count: 5
Design, Synthesis and hMAO Inhibitory Screening of Novel 2-Pyrazoline Analogues
(Bentham Science Publ Ltd, 2017) Yelekçi, Kemal; Uçar, Gülberk; Yelekçi, Kemal
Aim and Objective: MAO inhibitors have a significant effect on the nervous system since they act in regulation of neurotransmitter concentrations. Neurotransmitter levels are critical for a healthy nervous system. MAO inhibitors can be used in the treatment of neurological disorders such as depression, Parkinson's disease and Alzheimer's disease, as the increase or decrease of some neurotransmitter concentrations is associated with these neurological disorders. This study was conducted to discover new and active MAO inhibitor drug candidates. Materials and Methods: New pyrazoline derivatives have been designed with the molecular docking approach and interactions of our compounds with the MAO enzyme have been investigated using the Autodock 4.2 program. The designed pyrazoline derivative compounds were synthesized by the reaction of the chalcones and hydrazides in ethanol. hMAO inhibitory activities of the newly synthesized compounds were investigated by fluorimetric method. In vitro cytotoxicity of five most potent inhibitors were tested in HepG2 cells. Results: (3-(5-bromo-2-hydroxyphenyl)-5-(4-methoxyphenyl)-4,5-dihydropyrazol-1-yl)(phenyl) methanone (5i) and (3-(2-hydroxy-4-methoxy phenyl)-5-p-tolyl-4,5-dihydropyrazol-1-yl)(phenyl) methanone (5l) inhibited hMAO-A more potently than moclobemide (Ki values are 0.004 +/- 0.001 and 0.005 +/- 0.001, respectively). The same two compounds, 5i and 5l, inhibited hMAO-A more selectively than moclobemide (SI values are 5.55x10(-5) and 0.003, respectively). Both of these compounds were found non toxic at 1 mu M, 5 mu M and 25 mu M concentrations. Conclusion: Two of the newly synthesized compounds, (3-(5-bromo-2-hydroxyphenyl)-5-(4-methoxyphenyl)- 4,5-dihydropyrazol-1-yl)(phenyl) methanone and (3-(2-hydroxy-4-methoxy phenyl)5- p-tolyl-4,5-dihydropyrazol-1-yl)(phenyl) methanone were found to be promising MAO-A inhibitors due to their high inhibitory potency, high selectivity and low toxicity.
Citation Count: 5
Power of inhibition activity screening and 3D molecular modeling approaches in HDAC 8 inhibitor design
(Scientific Technical Research Council Turkey-Tubitak, 2011) Yelekçi, Kemal; Tokluman, Tenzile Deniz; Yelekçi, Kemal; Yurter, Hayat
In-vitro inhibition activity screening and in-silico 3D molecular modeling approaches are important tools for design and development of specific histone deacetylase (HDAC) inhibitors. The objective of this study was to investigate the consistency between these 2 approaches. The HDAC 8 inhibition activities of 8 randomly selected different carboxylic acid derivatives were screened and in-vitro experimental results were compared with in-silico molecular modeling calculations. This study demonstrated that there is no sole gold standard technique for inhibitor design and it was concluded that a combination of molecular modeling and activity screening assays will ensure more comprehensive and dependable results.
Potent inhibitors designed for methionine aminopeptidase II using pharmocophore modeling /
(Kadir Has Üniversitesi, 2019) Yelekçi, Kemal; Yelekçi, Kemal
Metaloenzimlerden Metiyonin Aminopeptidazlar (MetAP2), yeni sentezlenmiş polipep-titlerin başından metionin amino asidini kesmekle sorumludur. MetAP2'nin seçimli olarak engellenmesi damar oluşumunu baskıladığını, katı tümörlerde tümör boyunu ve metastazı sınırlandırdığı gösterilmiştir. Romatizma, kanser v.b. gibi tedavisi zor hastalıklarla direkt ilgili olduğu bulunmuştur. Araştırmacılar uzun süredir bu enzimi inhibe eden ilaçlar üzerine çalışmaktadır. Fumagillin MetAP2'nin doğal geri dönüşümsüz inhibitörüdür. Fumagillin ve yarı sentetik analogları potansiyel ilaç olarak umut vaat etmelerine karşı farmakokinetik ve nörotoksik özelliklerinden dolayı FDA'dan klinik deneyler için izin alamamıştır. Bu çalışmada, Zinc15 ve Ulusal Kanser Enstitüsü (NCI) veri bankalarından MatAP2'nin potansiyel ve tok- sik olmayan inhibitörleri in silico tarama, ligand ve yapı bazlı farmakofor modelleme yöntemleri ile elde edilmiştir. PyRx ve Doklama işlemleri ile uygulanarak aralarından daha isabetli ilaç adayları seçilmiştir. Discovery Studio (2016)'nın ADMET protokolü adayların farmakokinetik özelliklerini tespiti için kullanılmıştır. Bulunan bu adaylar MetAP2 enzimine potansiyel inhibitör olabilecekleri ve farmkokinetik özelliklerinin Fumagillian'dan daha iyi oldukları bulunmuştur. Bulunan bu moleküller biyolojik testler için ve tedavisi zor kanser ve bu gibi hastalıklara karşı çok iyi potansiyel ilaç adayları olacağı görüşüne varılmıştır. Methionine Aminopeptidase (Metap2) is a metalloenzyme that is responsible of removing of the N-terminal of newly synthesized protein. The inhibition of the enzyme was found to be crucial in diminishing tumor's nourishment, growth, and metastasis. It is directly related to incurable diseases such as Cancer, Rheumatoid Arthritis, etc. Over the year, different compounds were developed to inhibit that enzyme. Fumagillin, a natural irreversible inhibitor of MetAP2 and its derivatives, has been showing great potential therapy, however, their toxicity and poor pharmacokinetic characteristics have forbidden them from passing clinical trial and FDA approval. In this research, an in-silico approach was conducted to obtain a compound that is capable of inhibiting the enzyme with non-toxic properties. Two different approaches were conducted using a pharmacophore modeling; Ligand-Based, and Structure-Based. The Zinc15 and National Institute of Cancer Data (NCI) Databases was screened to obtain diversity of pre-synthesized compound. Followed by Molecular Docking filtration process using PyRx, and Autodock4. Followed by Discovery Studios protocol called ADMET prediction to signify the ability of these compound to pass the blood barriers and demonstrate batter pharmacokinetics properties than the Fumagillian. These compounds will serve, as Great Drug Candidate for the biological test in our continuous war against cancer and others Incurable disease.
Citation Count: 20
Synthesis and Screening of Human Monoamine Oxidase-A Inhibitor Effect of New 2-Pyrazoline and Hydrazone Derivatives
(Wiley-VCH Verlag GmbH, 2015) Yelekçi, Kemal; Baysal, İpek; Yabanoğlu-Çiftçi, Samiye; Djikic, Teodora; Yelekçi, Kemal; Uçar, Gülberk; Ertan, Rahmiye
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 compounds were tested for their inhibitory activities toward the A and B isoforms of human monoamine oxidase (MAO). Except for 3k and 6c all compounds were found to be competitive reversible and selective inhibitors for either one of the isoforms (hMAO-A or MAO-B). Compounds 3k and 6c were found to be competitive reversible but non-selective MAO inhibitors. Compound 6h showed hMAO-B inhibitory activity whereas the others potently inhibited hMAO-A. Compound 5c showed higher selectivity than the standard drug moclobemide. According to the experimental K-i values compounds 6i 6d and 6a exhibited the highest inhibitory activity toward hMAO-A. The AutoDock 4.2 program was employed to perform automated molecular docking. The calculated results obtained computationally were in good agreement with the experimental values.
In silico modeling of dopamine transporter and design of novel neuroprotective drugs for Parkinson's disease
(Kadir Has Üniversitesi, 2017) Yelekçi, Kemal; Yelekçi, Kemal
Parkinson hastalıgı (PH), substantia nigra (SN) ve corpus striatum (CS) bolgelerinde dopamin ureten noronların kaybedilmesi ile karakterize edilen bir olgudur. Yaygın olarak uygulanan tedavi dopamin noronlarının kaybolmalarının korunması yonunde degilde ortaya cıkan semtopların azaltılmasına yoneliktir. Insan dopamin tranporteri (hDAT) yoluyla spesifik olarak sinir hucresine alınan ve dopaminerjik noronları hedefleyen secici sinir koruyucu (noron protektif) ilaclar gecerli bir strateji olabilir. Tedavide dopaminin hucre dısı biyoaktif mikatını artırabilen dolayısı ile dopaminerjik norotransmisyonun kaybını dengeleyen ve kuvvetlendiren ve sitoplazmada birikerek noroprotektif olarak davranabilen molekuller gerekir. Bu calısmada homoloji modelleme, molekuler doklama ve molekuler dinamik simulasyon metodları kullanılarak substrat ve inhibitorle komplekslenmis hDAT'ın uc boyutlu (3D) yapı modelleri bulunmustur. Gelecekte yapılacak ilac tasarımlarında onemli olan bilesiklerin farklı baglanma kinetiklerini acıklayabilen hDAT'ın acık ve kapalı konformasyonları olusturulmustur. In silico yaklasımla elde edilmis olan yapılar bilesik veri bankası taraması sonucunda bize umit vadeden uc substrat molekulunun tespit edilmesine olanak saglamıstır. Bu substratların in vitro canlı hucre goruntu deneyleriyle hDAT'a dayalı fluoresan substratın hucreye geri girisi (uptake) inhibe etme etkileri de analiz edilmistir. Butun bu sonuclar birlikte degerlendirildiginde calısmamız in silico/in vitro yaklasımılarını birlikte kullanılarak dopaminerjik notron spesifik substratlların seciminde bir ilk model olusturmaktadır.