Esin Aki | Ankara University (original) (raw)

Papers by Esin Aki

Blood, 2015

Introduction and Aim: Myeloma plasma cells are dependent on stromal support which is mediated thr... more Introduction and Aim: Myeloma plasma cells are dependent on stromal support which is mediated through cell adhesion. Heparanase activity has been shown to be associated with aggressive behavior or Bortezomib resistance and can lead to increased levels of proteases as well as shedding of heparan sulfate proteoglycan syndecan-1(CD138) from myeloma cells. We have recently published in vivo anti-myeloma effects of low molecular weight heparin (Beksac et al Acta Haematol 2015). Protease activated Receptor (PAR1) is a thrombin receptor. PAR1 gene and antigen expression on myeloma patient samples and cell lines (HMCL) has been recently reported by University of Arkansas (UAMS) group (Tian et al ASH 2011). They were able to find HMCLs H929, U266, JJN3 to express PAR1. Also expression was found to be highest among patients with 5q amplification where the PAR1 gene is located. Patients and Methods: We analyzed PAR1 expression (WEDE15 PE, Beckman Coulter) by flow cytometry, on CD38+CD138+/-CD2...

Journal of Molecular Structure, 2001

Based on our contemporary studies on the structures of biologically active molecules, we focus ou... more Based on our contemporary studies on the structures of biologically active molecules, we focus our attention on the aliphatic chain and its conformation. That flexible spacer definitely influenced the balanced position of all pharmacophoric points in molecules of biological ligands. The one atomic linker and two or three atomic spacers with one heteroatom X = O, S, CH 2 , NH have been taken into account. The conformational preferences clearly depend on the heteroatom X. In the discussion, we utilize our own X-ray data, computation chemistry methods, population analysis, and statistical data from the Cambridge Structural Database (CSD).

Croatica Chemica Acta, 2013

Sar and Qsar in Environmental Research, 2008

$Research paper thumbnail of Vibrational spectroscopic (FT-IR, FT-Raman,<tex>^{1}H$</tex> NMR and UV) investigations and computational study of 5-nitro-2-(4-nitrobenzyl) benzoxazole$

Letters in Drug Design & Discovery

Molecular docking is a structure-based computational method that generates the binding pose and a... more Molecular docking is a structure-based computational method that generates the binding pose and affinity between ligands and targets. There are many powerful docking programs. However, there is no single program that is suitable for every system. Hence, an appropriate program is chosen based on availability, need, and computer capacity. Molecular docking has clear steps that should be followed carefully to get a good result. Molecular docking has many applications at various stages in drug discovery. Although it has various application areas, it is commonly applied in virtual screening and drug repurposing. As a result, it is playing a substantial role in the endeavor to discover a potent drug against COVID-19. There are also approved drugs in the pharmaceutical market that are developed through the use of molecular docking. As the accessible data is increasing and the method is advancing with the contribution of the latest computational developments, its use in drug discovery is al...

Letters in Drug Design & Discovery, 2018

RESUMO Objetivou-se com esse trabalho avaliar a eficiência do uso da água na produção de óleo do ... more RESUMO Objetivou-se com esse trabalho avaliar a eficiência do uso da água na produção de óleo do girassol sob suspensões hídricas. O experimento foi conduzido no Perímetro Irrigado Tabuleiros de Russas, situado no Vale Baixo do Jaguaribe. O delineamento utilizado foi o de blocos ao acaso, com quatro tratamentos e quatro repetições. Os tratamentos experimentais foram dispostos da seguinte maneira: sem ocorrência de suspensão (SS); suspensão iniciandose aos 35 DAP (S35); suspensão iniciando-se aos 50 DAP (S50); suspensão iniciando-se aos 65 DAP (S65). Foram avaliadas as seguintes variáveis: eficiência do uso da água em produzir aquênios (EUA AQUÊNIOS), teor de óleo dos aquênios (TOA), produtividade potencial de óleo (PPO) e eficiência do uso da água em produzir óleo (EUA PPO). Pela análise de variância observou-se que TOA não sofreu inferência estatística em função dos tratamentos analisados, diferentemente da PPO, EUA PPO e a EUA AQUÊNIOS que sofreram a influência dos tratamentos aplicados, ao nível de 5% de probabilidade pelo teste F. Nas condições climáticas na qual foi desenvolvido o experimento, o aumento da suspensão hídrica provocou queda na produtividade potencial de óleo. A eficiência do uso da água em produzir óleo e aquênios aumentou conforme a cultura foi exposta a restrição de água.

DARU Journal of Pharmaceutical Sciences, 2019

Background The numbers of topoisomerase I targeted drugs on the market are very limited although ... more Background The numbers of topoisomerase I targeted drugs on the market are very limited although they are used clinically for treatment of solid tumors. Hence, studies about finding new chemical structures which specifically target topoisomerase I are still remarkable. Objectives In this present study, we tested previously synthesized 3,4-dihydro-2H-1,4-benzoxazin-3-one derivatives to reveal their human DNA topoisomerase I inhibitory potentials. Methods We investigated inhibitory activities of 3,4-dihydro-2H-1,4-benzoxazin-3-one derivatives on human topoisomerase I by relaxation assay to clarify inhibition mechanisms of effective derivatives with EMSA and T4 DNA ligase based intercalation assay. With SAR study, it was tried to find out effective groups in the ring system. Results While 10 compounds showed catalytic inhibitory activity, 8 compounds were found to be potential topoisomerase poisons. 4 of them also exhibited both activities. 2-hydroxy-3,4-dihydro-2H-1,4-benzoxazin-3-one (BONC-001) was the most effective catalytic inhibitor (IC 50 :8.34 mM) and ethyl 6-chloro-4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-acetate (BONC-013) was the strongest potential poison (IC 50 :0.0006 mM). BONC-013 was much more poisonous than camptothecin (IC 50 :0.034 mM). Intercalation assay showed that BONC-013 was not an intercalator and BONC-001 most probably prevented enzyme-substrate binding in an unknown way. Another important result of this study was that OH group instead of ethoxycarbonylmethyl group at R position of benzoxazine ring was important for hTopo I catalytic inhibition while the attachment of a methyl group of R1 position at R 2 position were play a role for increasing of its poisonous effect. Conclusion As a result, we presented new DNA topoisomerase I inhibitors which might serve novel constructs for future anticancer agent designs. Keywords Benzoxazine. Anticancer. Topoisomerase I. Catalytic inhibitor. Topoisomerase I poison Key-Points • Benzoxazine derivatives inhibit human DNA topoisomerase I action. • BONC-001 inhibited catalytic activity of hTopo I by interacting with DNA binding site of the enzyme. • OH group at the 2nd position of benzoxazine ring was very important for catalytic inhibition. • BONC-013, 77 times more effective than CPT, inhibited hTopo I activity by stabilizing covalent enzyme-DNA complex. • The attachment of methyl group of the R1 position seemed to play a role for poison effect.

Chemical Biology & Drug Design, 2018

Homology modeling is one of the computational structure prediction methods that are used to deter... more Homology modeling is one of the computational structure prediction methods that are used to determine protein 3D structure from its amino acid sequence. It is considered to be the most accurate of the computational structure prediction methods. It consists of multiple steps that are straightforward and easy to apply. There are many tools and servers that are used for homology modeling. There is no single modeling program or server which is superior in every aspect to others. Since the functionality of the model depends on the quality of the generated protein 3D structure, maximizing the quality of homology modeling is crucial. Homology modeling has many applications in the drug discovery process. Since drugs interact with receptors, which consists mainly of proteins in their structure, protein 3D structure determination, and thus homology modeling is important in drug discovery. Accordingly, there has been the clarification of protein interactions using 3D structures of proteins that are built with homology modeling. This contributes to the identification of novel drug candidates. Homology modeling plays an important role in making drug discovery faster, easier, cheaper and more practical. As new modeling methods and combinations are introduced, the scope of its applications widens.

SAR and QSAR in Environmental Research, 2017

Abstract Acinetobacter baumannii has emerged as an important pathogen for nosocomial infections h... more Abstract Acinetobacter baumannii has emerged as an important pathogen for nosocomial infections having high morbidity and mortality. This pathogen is notorious for antimicrobial resistance to many common antimicrobial agents including fluoroquinolones, which have both intrinsic and acquired resistance mechanisms. Fluoroquinolones targeting the bacterial topoisomerase II (DNA gyrase and Topo IV) show potent broad-spectrum antibacterial activity by the stabilization of the covalent enzyme–DNA complex. However, their efficacy is now being threatened by an increasing prevalence of resistance. Fluoroquinolones cause stepwise mutations in DNA gyrase and Topo IV, having alterations of their binding sites. Furthermore, the water–Mg+2 bridge, which provides enzyme–fluoroquinolone interactions, has a significant role in resistance. In this study, 13 compounds were synthesized as 1,4-benzoxazine derivatives which act as bacterial topoisomerase II inhibitors and their antibacterial activities were determined against multi-drug resistant Acinetobacter strains which have ciprofloxacin (CIP) resistant and GyrA mutation. Afterwards we performed docking studies with Topo IV (pdb:2XKK) of these compounds to comprehend their binding properties in Discovery Studio 3.5. The results of this study show significant conclusions to elucidate the resistance mechanism and lead to the design of new antibacterial agents as bacterial topoisomerase II inhibitors.

European Journal of Medicinal Chemistry, 2006

This article was originally published in a journal published by Elsevier, and the attached copy i... more This article was originally published in a journal published by Elsevier, and the attached copy is provided by Elsevier for the author's benefit and for the benefit of the author's institution, for non-commercial research and educational use including without limitation use in instruction at your institution, sending it to specific colleagues that you know, and providing a copy to your institution's administrator.

SAR and QSAR in environmental research, Jan 26, 2015

Protease-activated receptor 1 (PAR1) has been established as a promising target in many diseases,... more Protease-activated receptor 1 (PAR1) has been established as a promising target in many diseases, including various cancers. Strong evidence also suggests its role in metastasis. It is proved experimentally that PAR1 can induce numerous cell phenotypes, i.e. proliferation and differentiation. A strong link between PAR1 gene overexpression and high levels of ß-catenin was suggested by a study of the PAR1-Gα(13)-DVL axis in ß-catenin stabilization in cancers. An in vitro study was carried out to analyze PAR1 expression by flow cytometry on CD38+138+ plasma cells obtained from patients either at diagnosis (n: 46) (newly diagnosed multiple myeloma (NDMM)) or at relapse (n: 45) (relapsed/refractory multiple myeloma (RRMM)) and compared with the controls. Our previously synthesized benzoxazole (XT2B) and benzamide (XT5) derivatives were tested with in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, which revealed significant inhibitory activity on PAR1. We...

ChemMedChem, 2019

AFMC-AIMECS meetings are internationally organized biannually by the Asian Federation for Medicin... more AFMC-AIMECS meetings are internationally organized biannually by the Asian Federation for Medicinal Chemistry (AFMC) and are focused on recent studies in drug discovery and development both in academia and industry. Member organizations of the AFMC are the Pharmaceutical Society of Japan,

Croatica Chemica Acta, 2017

β-Lactam antibiotics are frequently used for treatment of multi-drug resistant microbial infectio... more β-Lactam antibiotics are frequently used for treatment of multi-drug resistant microbial infections and the most common mechanism of resistance against these antibiotics is bacterial β-lactamase production. Herein, we reported the design, synthesis and in vitro antimicrobial activities of some new 2-substituted-5-(2,4-dinitrophenylsulfonamido)benzoxazole derivatives. Compounds TN1, TN2, and TN3 were found to be significantly active against E. coli isolate which contains extended spectrum β-lactamase enzyme at the MIC value of 8 µg mL-1 and that is 4-fold higher than the reference drug ampicillin. We performed molecular docking studies into active site of Escherichia coli TEM-1 β-lactamase enzyme in order to predict the protein-ligand interactions. According to the docking results, compounds TN1, TN2, and TN3 showed strong interactions between the important active site residues which are responsible for the catalytic mechanism of TEM-1 β-lactamase enzyme and a good correlation is found with the experimental data.

$Research paper thumbnail of Frequency Of Protease Activated Receptor1 (PAR1) Expression And The In Vitro Effects Of XT5 And XT2B, Two Novel PAR1 Binding Molecules, On Primary And Bortezomib Refractory Myeloma Cell Lines$

Clinical Lymphoma Myeloma and Leukemia, 2015

European Journal of Medicinal Chemistry, 2008

The synthesis and antimicrobial activity of a new series of 5-ethylsulphonyl-2-(substituted-pheny... more The synthesis and antimicrobial activity of a new series of 5-ethylsulphonyl-2-(substituted-phenyl/substituted-benzyl and/or phenylethyl)benzoxazole derivatives (3ae3t) except 3a, 3g, 3h, 3k [R.

Journal of Pharmacy and Pharmacology, 2017

Recently, NK1R (Neurokinin-1 receptors) take attention as new and promising target in anticancer ... more Recently, NK1R (Neurokinin-1 receptors) take attention as new and promising target in anticancer drug development area. It has been proved that non-peptide NK1R antagonists L-733,060, aprepitant and L-732,138 inhibited tumor growth in several cancer cell lines. For the development of novel NK1R antagonists as antitumor agents, heterocyclic compounds which were previously synthesized by our team, tested for their cytotoxic activities in several cancer cell lines in this study. Among the tested compounds, a benzothiazole derivative BSN-009 inhibited colon cancer cell lines growth by 57.53% by comparing the activity to the control drug aprepitant. Molecular modeling studies such as molecular docking and pharmacophore generation were performed with known NK1R antagonists and BSN-009 by using Discovery Studio 3.5 in order to explain their binding modes to NK1R. BSN-009 may be a good anticancer drug candidate as a possible NK1R antagonist and is worthy to carry on the anticancer studies.