Identification of hCA I, hCA II, AChE and BChE Inhibitory Properties of Some Norcantharimide Derivatives; Molecular Docking, SAR and in silico ADME Studies Leyla Polat Köse, Aytekin Köse Chemistryselect, 2024 (3aR,4S,7R,7aS)‐2‐Alkyl/aryl‐3a,4,7,7a‐tetrahydro‐1H‐4,7‐epoxyisoindole‐1,3(2H)‐diones, which are norcantharimide derivatives, were synthesized and their effects on carbonic anhydrase I (hCA I) and II (hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activity were investigated. For enzyme activity studies, hCA I and II isoenzymes purified from human erythrocytes and the commercially available enzymes AChE and BChE, which are both markers and significantly affect the known symptoms of Alzheimer's disease, were used. The two derivatives exerted efficient inhibition with IC50=4.530 nM (Ki=4.483) and 4.426 nM (Ki=4.696) against hCA I and with IC50=3.825 nM (Ki=3.854) and 3.457 nM (Ki=3.292) against hCA II, respectively. The another two derivatives exerted considerable inhibition with IC50=0.526 nM (Ki=0.224) and 0.575 nM (Ki=0.292) against AChE and with IC50=0.135 nM (Ki=0.057) and IC50=0.180 nM (Ki=0.070) against BChE, respectively. The compounds showed activity at the nanomolar level. These remarkable inhibition results were compared with those of standard inhibitors (acetazolamide for hCA I and II and tacrine for AChE and BChE) of each enzyme, reported, and graphed. In addition, molecular docking studies were carried out by in silico methods and the structure–activity relationship was discussed. The poses of compound 4 c are presented along with the ligand–receptor interaction against all metabolic enzymes.
Synthesis and Anticancer Activity of Novel Derivatives of α,β-Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer Cells Halil Şenol, Mansour Ghaffari‐Moghaddam, Şeyma Bulut, Fahri Akbaş, Aytekin Köse, Gülaçtı Topçu Chemistry and Biodiversity, 2023 Herein, new derivatives of α,β‐unsaturated ketones based on oleanolic acid (4 a–i) were designed, synthesized, characterized, and tested against human prostate cancer (PC3). According to the in vitro cytotoxic study, title compounds (4 a–i) showed significantly lower toxicity toward healthy cells (HUVEC) in comparison with the reference drug doxorubicin. The compounds with the lowest IC50 values on PC3 cell lines were 4 b (7.785 μM), 4 c (8.869 μM), and 4 e (8.765 μM). The results of the ADME calculations showed that the drug‐likeness parameters were within the defined ranges according to Lipinski's and Jorgensen's rules. For the most potent compounds 4 b, 4 c, and 4 e, a molecular docking analysis using the induced fit docking (IFD) protocol was performed against three protein targets (PARP, PI3K, and mTOR). Based on the IFD scores, compound 4 b had the highest calculated affinity for PARP1, while compound 4 c had higher affinities for mTOR and PI3K. The MM‐GBSA calculations showed that the most potent compounds had high binding affinities and formed stable complexes with the protein targets. Finally, a 50 ns molecular dynamics simulation was performed to study the behavior of protein target complexes under in silico physiological conditions.
Evaluation of In Vivo Biological Activity Profiles of Isoindole-1,3-dione Derivatives: Cytotoxicity, Toxicology, and Histopathology Studies Aytekin Köse, Meltem Kaya, Canberk Tomruk, Yiǧit Uyanıkgil, Nurhan Kishalı, Yunus Kara, Gülşah Şanlı-Mohamed ACS Omega, 2023 The anticancer activity of N-benzylisoindole-1,3-dione derivatives was evaluated against adenocarcinoma (A549-Luc). First, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide activity assay studies of two isoindole-1,3-dione derivatives were performed against A549 cell lines. Both compounds showed inhibitory effects on the viability of A549 cells. Then, we explored the potential of these compounds as active ingredients by in vivo studies. Nude mice were given A549-luc lung cancer cells, and tumor growth was induced with a xenograft model. Then, nude mice were divided into three groups: the control group, compound 3 group, and compound 4 group. After application of each compound to the mice, tumor sizes, their survival, and weight were determined for 60 days. Furthermore, toxicological studies were performed to examine the effects of the drugs in mice. In addition to toxicological studies, histopathological analyses of organs taken from mice were performed, and the results were evaluated. The obtained results showed that both N-benzylisoindole derivatives are potential anticancer agents.
Investigation of cytotoxic properties of some isoindole-related compounds bearing silyl and azide groups with in vitro and in silico studies Ayşe Tan, Aytekin Köse, Derya Mete, Gülşah Şanlı-Mohamed, Nurhan H. Kishalı, Yunus Kara Phosphorus Sulfur and Silicon and the Related Elements, 2023 This study aims to evaluate the synthesis of isoindole-1,3-dione analogues and their cytotoxic potential. A549 and HeLa cells exposed to 250–100–50–25 µM doses of each derivative were incubated for 24, 48, and 72 h. The cytotoxicity of the isoindole-1,3-dione derivatives was analyzed using the cell growth inhibition assay and the cell membrane damage test. (3aR,5R,6R,7aS)-5-Azido-2-benzyl-6-hydroxyhexahydro-1H-isoindole-1,3(2H)-dione (1d), (3aR,5R,6R,7aS)-5-azido-6-((tert-butyldiphenylsilyl)oxy)-2-ethylhexahydro-1H-isoindole-1,3(2H)-dione (2a), and (3aR,5R,6R,7aS)-5-azido-6-((tert-butyldiphenylsilyl)oxy)-2-methylhexahydro-1H-isoindole-1,3(2H)-dione (2b) compounds inhibited the growth of the A549 and HeLa cells caused membrane damage and exhibited a dose-dependent cytotoxic effect on lung and cervical carcinoma cells. The effect of tert-butyldiphenylsilyl (TBDPS) groups on cytotoxicity was observed in compounds 2a and 2b, but not in the other compounds. Considering the effect of groups attached to the nitrogen atom, the best activity was exhibited in 2b molecule to which the methyl group is attached. Additionally, the interactions of compounds (3aR,5R,6R,7aS)-5-azido-6-hydroxy-2-methylhexahydro-1H-isoindole-1,3(2H)-dione (1b), 1d, 2a and 2b with mammalian rapamycin target, human ribosomal S6 kinase 1 and human epidermal growth factor receptor were investigated by molecular docking studies, . According to the docking results, 2a and 2b compounds containing a TBDPS group have stronger binding energies than 1b and 1d compounds against all target receptors. GRAPHICAL ABSTRACT
4-(2, 4-dichlorobenzamido)-benzohydrazide derivatives and their elastic liposomal formulations for cholinesterase and neuroblastoma inhibition: A comprehensive in vitro and in … F Çakır, AG Ağgül, AM Şenol, HŞ Bektay, M Gökçe, A Köse, ... Journal of Molecular Structure, 146575 , 2026 2026
Novel Triazole linked thymol-thienopyrimidine hybrids: In vitro and in silico studies Ş Ateşoğlu, F Çakır, A Köse, F Akbaş, ZŞ Bilgiseven, H Şenol 2025
Antiviral activities of phenylalanine derivatives carrying carboxylic acid bioisosteres against chikungunya and parainfluenza virus type 3 MC Eren, G Güngör, S De Jonghe, D Jochmans, M Özbil, J Neyts, ... Bioorganic & Medicinal Chemistry, 118343 , 2025 2025 Citations: 1
Antiviral activities of phenylalanine derivatives carrying carboxylic acid bioisosteres against chikungunya and parainfluenza virus type 3 G Güngör, S De Jonghe, D Jochmans, M Özbil, J Neyts, S Kaptein, ... 2025
New 4-methanesulfonyloxy benzohydrazide derivatives as potential antioxidant and carbonic anhydrase I and II inhibitors: synthesis, characterization, molecular docking … A Köse, LP Köse, H Şenol, N Ulusoy-Güzeldemirci Journal of Molecular Structure 1325, 140937 , 2025 2025 Citations: 12
Novel 4-((3-fluorobenzyl) oxy) benzohydrazide derivatives as promising anti-prostate cancer agents: synthesis, characterization and in vitro & in Silico biological activity studies F Çakır, Ş Ateşoğlu, A Köse, M Ghaffari-Moghaddam, F Akbaş, H Kınay, ... Journal of Molecular Structure 1322, 140702 , 2025 2025 Citations: 34
Antiviral activities of phenylalanine derivatives carrying carboxylic acid bioisosteres against chikungunya and parainfluenza virus type 3 M Camcı Eren, G Güngör, S De Jonghe, D Jochmans, M Özbil, J Neyts, ... BIOORGANIC AND MEDICINAL CHEMISTRY 129 , 2025 2025
Bioisosteric replacement of the carboxylic acid group in Hepatitis-C virus NS5B thumb site II inhibitors: phenylalanine derivatives M Camci, H Şenol, A Kose, BK Mayack, MM Alayoubi, N Karali, ... European Journal of Medicinal Chemistry 279, 116832 , 2024 2024 Citations: 9
Identification of hCA I, hCA II, AChE and BChE Inhibitory Properties of Some Norcantharimide Derivatives; Molecular Docking, SAR and in silico ADME Studies L Polat Köse, A Köse ChemistrySelect 9 (16), e202400684 , 2024 2024 Citations: 4
Basic and Simple Step Synthesis and Characterization of Novel Hydrazide Derivatives Containing 4-Methylsulfonate Ester Scaffold A Köse, H Şenol, N Ulusoy-Güzeldemirci 2024
Nükleozid Yapılı Olmayan Yeni HCV-NS5B RNA Polimeraz İnhibitörlerinin Tasarımı, Sentezi ve Biyolojik Aktivitelerinin İncelenmesi M CAMCI Eczacılık Fakültesi , 2024 2024
Investigation of cytotoxic properties of some isoindole-related compounds bearing silyl and azide groups with in vitro and in silico studies A Tan, A Köse, D Mete, G Şanlı-Mohamed, NH Kishalı, Y Kara Phosphorus, Sulfur, and Silicon and the Related Elements 198 (11), 933-942 , 2023 2023 Citations: 2
Synthesis and Anticancer Activity of Novel Derivatives of α,β‐Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer … H Şenol, M Ghaffari‐Moghaddam, Ş Bulut, F Akbaş, A Köse, G Topçu Chemistry & biodiversity 20 (9), e202301089 , 2023 2023 Citations: 45
Investigation Into The Molecular Stability, Synthesis Mechanism, and Formation of Some Norcantharimide Derivatives Using AcCl or Ac2O: A Mechanism-Based Study A Köse Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 23 (3), 618-627 , 2023 2023
Evaluation of In Vivo Biological Activity Profiles of Isoindole-1, 3-dione Derivatives: Cytotoxicity, Toxicology, and Histopathology Studies A Kose, M Kaya, C Tomruk, Y Uyanıkgil, N Kishalı, Y Kara, ... Acs Omega 8 (13), 12512-12521 , 2023 2023 Citations: 2
Unique reaction of cyclicimides containing double bond with chlorosulfonyl isocyanate and theoretical computations: Solvent-free reactions A Köse, E Soydaş, Y Kara Journal of Molecular Structure 1274, 134428 , 2023 2023 Citations: 2
4-((3-(Triflorometil) piridin-2-il) oksi) benzohidrazit Birimi İçeren Yeni Hidrazon Türevlerinin Sentezi A Köse Journal of the Institute of Science and Technology 11 (4), 2870-2879 , 2021 2021
A simple route for the synthesis of novel norcantharimide derivatives via acidolysis with hydrochloric acid (gas) A Köse Journal of Heterocyclic Chemistry 58 (5), 1171-1178 , 2021 2021
Synthesis and biological evaluation of new chloro/acetoxy substituted isoindole analogues as new tyrosine kinase inhibitors A Köse, M Kaya, NH Kishalı, A Akdemir, E Şahin, Y Kara, ... Bioorganic Chemistry 94, 103421 , 2020 2020 Citations: 18
An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS, 7aR, E)-2-ethyl-3-oxo-2, 3, 3a, 4, 7, 7a-hexahydro-1H-isoindol-1-ylidene … A Köse, A Ünal, E Şahin, U Bozkaya, Y Kara Beilstein Journal of Organic Chemistry 15 (1), 931-936 , 2019 2019 Citations: 4
MOST CITED SCHOLAR PUBLICATIONS
Synthesis and Anticancer Activity of Novel Derivatives of α,β‐Unsaturated Ketones Based on Oleanolic Acid: in Vitro and in Silico Studies against Prostate Cancer … H Şenol, M Ghaffari‐Moghaddam, Ş Bulut, F Akbaş, A Köse, G Topçu Chemistry & biodiversity 20 (9), e202301089 , 2023 2023 Citations: 45
Novel 4-((3-fluorobenzyl) oxy) benzohydrazide derivatives as promising anti-prostate cancer agents: synthesis, characterization and in vitro & in Silico biological activity studies F Çakır, Ş Ateşoğlu, A Köse, M Ghaffari-Moghaddam, F Akbaş, H Kınay, ... Journal of Molecular Structure 1322, 140702 , 2025 2025 Citations: 34
Synthesis and anticancer activity evaluation of new isoindole analogues A Köse, Y Bal, NH Kishalı, G Şanlı-Mohamed, Y Kara Medicinal Chemistry Research 26 (4), 779-786 , 2017 2017 Citations: 31
Synthesis and biological evaluation of new chloro/acetoxy substituted isoindole analogues as new tyrosine kinase inhibitors A Köse, M Kaya, NH Kishalı, A Akdemir, E Şahin, Y Kara, ... Bioorganic Chemistry 94, 103421 , 2020 2020 Citations: 18
New 4-methanesulfonyloxy benzohydrazide derivatives as potential antioxidant and carbonic anhydrase I and II inhibitors: synthesis, characterization, molecular docking … A Köse, LP Köse, H Şenol, N Ulusoy-Güzeldemirci Journal of Molecular Structure 1325, 140937 , 2025 2025 Citations: 12
Bioisosteric replacement of the carboxylic acid group in Hepatitis-C virus NS5B thumb site II inhibitors: phenylalanine derivatives M Camci, H Şenol, A Kose, BK Mayack, MM Alayoubi, N Karali, ... European Journal of Medicinal Chemistry 279, 116832 , 2024 2024 Citations: 9
Enantiospecific Synthesis of ( R )‐3‐Amino‐4‐(2,4,5‐trifluorophenyl)butanoic Acid Using ( S )‐Serine as a Chiral Pool A Köse, Ö Gündoğdu, D Aktaş, M Fıstıkçı, R Altundaş, H Secen, Y Kara Helvetica Chimica Acta 98 (2), 260-266 , 2015 2015 Citations: 6
Nucleophilic Reactivity of Ethers Against Terminal Epoxides in the Presence of BF 3 : A Mechanistic Study A Kose, R Altundas, H Seçen, Y Kara Helvetica Chimica Acta 96 (7), 1325-1330 , 2013 2013 Citations: 5
Identification of hCA I, hCA II, AChE and BChE Inhibitory Properties of Some Norcantharimide Derivatives; Molecular Docking, SAR and in silico ADME Studies L Polat Köse, A Köse ChemistrySelect 9 (16), e202400684 , 2024 2024 Citations: 4
An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS, 7aR, E)-2-ethyl-3-oxo-2, 3, 3a, 4, 7, 7a-hexahydro-1H-isoindol-1-ylidene … A Köse, A Ünal, E Şahin, U Bozkaya, Y Kara Beilstein Journal of Organic Chemistry 15 (1), 931-936 , 2019 2019 Citations: 4
Reaction of (S)-homoserine lactone with Grignard reagents: synthesis of amino-keto-alcohols and β-amino acid derivatives Ö Gündoğdu, P Turhan, A Köse, R Altundaş, Y Kara Tetrahedron: Asymmetry 28 (9), 1163-1168 , 2017 2017 Citations: 3
Investigation of cytotoxic properties of some isoindole-related compounds bearing silyl and azide groups with in vitro and in silico studies A Tan, A Köse, D Mete, G Şanlı-Mohamed, NH Kishalı, Y Kara Phosphorus, Sulfur, and Silicon and the Related Elements 198 (11), 933-942 , 2023 2023 Citations: 2
Evaluation of In Vivo Biological Activity Profiles of Isoindole-1, 3-dione Derivatives: Cytotoxicity, Toxicology, and Histopathology Studies A Kose, M Kaya, C Tomruk, Y Uyanıkgil, N Kishalı, Y Kara, ... Acs Omega 8 (13), 12512-12521 , 2023 2023 Citations: 2
Unique reaction of cyclicimides containing double bond with chlorosulfonyl isocyanate and theoretical computations: Solvent-free reactions A Köse, E Soydaş, Y Kara Journal of Molecular Structure 1274, 134428 , 2023 2023 Citations: 2
Antiviral activities of phenylalanine derivatives carrying carboxylic acid bioisosteres against chikungunya and parainfluenza virus type 3 MC Eren, G Güngör, S De Jonghe, D Jochmans, M Özbil, J Neyts, ... Bioorganic & Medicinal Chemistry, 118343 , 2025 2025 Citations: 1
4-(2, 4-dichlorobenzamido)-benzohydrazide derivatives and their elastic liposomal formulations for cholinesterase and neuroblastoma inhibition: A comprehensive in vitro and in … F Çakır, AG Ağgül, AM Şenol, HŞ Bektay, M Gökçe, A Köse, ... Journal of Molecular Structure, 146575 , 2026 2026
Novel Triazole linked thymol-thienopyrimidine hybrids: In vitro and in silico studies Ş Ateşoğlu, F Çakır, A Köse, F Akbaş, ZŞ Bilgiseven, H Şenol 2025
Antiviral activities of phenylalanine derivatives carrying carboxylic acid bioisosteres against chikungunya and parainfluenza virus type 3 G Güngör, S De Jonghe, D Jochmans, M Özbil, J Neyts, S Kaptein, ... 2025
Antiviral activities of phenylalanine derivatives carrying carboxylic acid bioisosteres against chikungunya and parainfluenza virus type 3 M Camcı Eren, G Güngör, S De Jonghe, D Jochmans, M Özbil, J Neyts, ... BIOORGANIC AND MEDICINAL CHEMISTRY 129 , 2025 2025
Basic and Simple Step Synthesis and Characterization of Novel Hydrazide Derivatives Containing 4-Methylsulfonate Ester Scaffold A Köse, H Şenol, N Ulusoy-Güzeldemirci 2024
