WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
Browse
8 results
Search Results
Now showing 1 - 8 of 8
Article Anticancer Properties of Newly Synthesized Pyrrole Derivatives as Potential Tyrosine Kinase Inhibitors(Wiley, 2026) Kaya, Meltem; Kara, Yunus; Sanli-Mohamed, GulsahThe anticancer activity of a series of newly synthesized pyrrole derivatives was systematically evaluated in HeLa cervical cancer cells, focusing on their potential as tyrosine kinase inhibitors and modulators of the mTOR signaling pathway. This study builds on our previous synthetic work by investigating the biological effects of seven structurally characterized compounds (d1-d7). Among them, compounds d1 and d3 exhibited the most potent cytotoxicity, with IC50 values of 140.6 mu M and 366.4 mu M, respectively, after 48 h of treatment. Both compounds significantly impaired cell cycle progression-d1 induced S-phase arrest, while d3 caused G1-phase arrest-and markedly suppressed cell migration in wound healing assays. Mechanistically, these effects were accompanied by reduced phosphorylation of p70S6K (Thr389, Ser421/424) and increased p-4EBP1, indicating inhibition of mTORC1 signaling. These findings suggest that d1 and d3 are promising lead compounds with dual antiproliferative and anti-migratory activity in cervical cancer, mediated through modulation of the PI3K/Akt/mTOR axis.Article Assessment of Cytotoxic Potentials of Isoindole-Derived Compounds With Epoxy Alcohol Functionalities on Different Cancer Cell Lines and Molecular Docking Analysis(Maik Nauka/Interperiodica/Springer, 2025) Yetiskin, Egehan; Gundogdu, Ozlem; Mete, Derya; Kishali, Nurhan H.; Kara, Yunus; Sanli-Mohamed, GulsahObjective: Isoindoline and epoxycyclohexane derivatives are known to exert beneficial effects on various inflammatory pathologies, including cancer. This study uniquely evaluates the cytotoxic potential of four synthesized isoindoline derivatives against five different cancer cell lines. Methods: Cancer cell lines were treated with varying concentrations of each derivative and incubated for 24, 48, and 72 h. Cytotoxicity was assessed via cell growth inhibition assays and cell membrane damage tests. Additionally, molecular docking studies were conducted to examine the interaction of the compounds with key cancer-related proteins: human tankyrase 1, c-MET, estrogen receptor alpha, androgen receptor, and EGFR. Results and Discussion: The epoxy alcohol derivatives demonstrated a dose-dependent cytotoxic effect, inhibited cell proliferation, and induced membrane damage in adenocarcinoma cell lines. Apoptosis rates and in vitro wound healing assays further supported their antiproliferative potential. Conclusions: These findings suggest that epoxy isoindole derivatives may serve as promising anticancer agents for the treatment of cervical, lung, prostate, and breast cancers due to their cytotoxic and antiproliferative activities. Molecular docking results corroborated their potential mechanism of action.Article Citation - WoS: 3Citation - Scopus: 3Synthesis, Cytotoxicity, and Antibacterial Studies of 2,4,5,6-Substituted Hexahydro-1h(Wiley, 2023) Yetişkin, Egehan; Gündoğdu, Özlem; Mete, Derya; Celebioglu, Neslihan; Kara, Yunus; Şanlı-Mohamed, GulsahIn this study, synthesis of novel isoindole-1,3-dione analogues bearig halo, hydroxy, and acetoxy groups at the position 4,5,6 of the bicyclic imide ring was performed to examine their potential anticancer effects against some cell lines. A multistep chemical pathway was used to synthesize the derivatives. The cytotoxic effect of trisubstituted isoindole derivatives were evaluated by determining cellular viability using the MTT assay against A549, PC-3, HeLa, Caco-2, and MCF-7 cell lines. The C-2 selective ring-opening products were obtained from the ring-opening reaction of 5-alkyl/aryl-2-hydroxyhexahydro-4H-oxireno[2,3-e]isoindole-4,6(5H)-diones with nucleophiles such as chloride (Cl-) and bromide (Br-) ions. In addition, the ring-opening products halodiols were converted to their related acetates. The anticancer activity of synthesized isoindole-1,3-dione derivatives was investigated against HeLa, A549, MCF-7, PC3, and Caco-2 cells in vitro and resulted in varies cytotoxic effect depend on the group attached to the isoindole molecule. Furthermore, the evaluation of the antimicrobial action of trisubstituted isoindole derivatives against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria was assessed and found out selective inhibition of the both bacterial growth via different trisubstituted isoindole derivatives. The results of this work encourage further research on the potential utilization of trisubstituted isoindole derivatives as cytotoxic and antimicrobial agents.Article Citation - WoS: 1Citation - Scopus: 1Investigation of Cytotoxic Properties of Some Isoindole-Related Compounds Bearing Silyl and Azide Groups With in Vitro and in Silico Studies(Taylor & Francis, 2023) Tan, Ayşe; Köse, Aytekin; Mete, Derya; Şanlı Mohamed, Gülşah; Kışhalı, Nurhan H.; Kara, YunusThis 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 mu M 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.Article Citation - WoS: 1Citation - Scopus: 2Evaluation of in Vivo Biological Activity Profiles of Isoindole-1,3 Derivatives: Cytotoxicity, Toxicology, and Histopathology Studies(Amer Chemical Soc, 2023) Köse, Aytekin; Kaya, Meltem; Tomruk, Canberk; Uyanıkgil, Yiğit; Kıshalı, Nurhan; Kara, Yunus; Şanlı Mohamed, GülşahThe 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.Article Citation - WoS: 7Citation - Scopus: 7Regio- and Stereo-Chemical Ring-Opening Reactions of the 2,3-Epoxy Alcohol Derivative With Nucleophiles: Explanation of the Structures and C-2 Selectivity Supported by Theoretical Computations(Elsevier, 2022) Gündoğdu, Özlem; Atalay, Abdurrahman; Çelebioğlu, Neslihan; Anıl, Barış; Şahin, Ertan; Şanlı Mohamed, Gülşah; Bozkaya, Uğur; Kara, YunusThe ring-opening reactions of (1aS,2S,6bR)-5-ethyl-2-hydroxyhexahydro-4H-oxireno[2,3-e]isoindole-4,6(5H)-dione were investigated under very mild and nonchelated conditions. C-2 selective ring-opening products were obtained with nucleophilic additions such as Cl−, Br− and N3−. The exact configuration of (3aS,4R,5R,6S,7aS)-5-chloro-2-ethyl-4,6-dihydroxyhexahydro-1H-isoindole-1,3(2H)-dione was determined by X-Ray diffraction analysis which was obtained from the reaction of epoxy alcohol with HCl. On the other hand, theoretical computations were carried out to explain the regioselectivity in the ring opening reaction of epoxy alcohols. The results showed that the ring-opening reaction of both epoxy alcohols proceeds in a kinetically controlled manner and regioselectivity occurs depending on the transition state.Article Citation - WoS: 12Citation - Scopus: 13Synthesis and Biological Evaluation of New Chloro/Acetoxy Substituted Isoindole Analogues as New Tyrosine Kinase Inhibitors(Academic Press, 2020) Köse, Aytekin; Kaya, Meltem; HorasanKishalı, Nurhan; Akdemir, Atilla; Şahin, Ertan; Kara, Yunus; Şanlı Mohamed, GülşahWe have developed a versatile synthetic approach for the synthesis of new isoindole derivatives via the cleavage of ethers from tricyclic imide skeleton compounds. An exo-cycloadduct prepared from the Diels-Alder reaction of furan and maleic anhydride furnished imide derivatives. The epoxide ring was opened with Ac2O or Ac2O/AcCl in the presence of a catalytic amount of H2SO4 in order to yield new isoindole derivatives 8a-d and 9a-d. The anticancer activity of these compounds was evaluated against the HeLa cell lines. The synthesized compounds showed inhibitory effects on the viability of HeLa cells and the degree of cytotoxicity was increased with the level of bigger branched isoindole derivatives. To better understand the acting mechanism of these molecules, western blot analysis was performed with using mTOR and its downstream substrates. In addition, human mTOR and ribozomal S6 kinase beta 1 (RS6K beta 1) have been investigated with molecular modelling studies as possible targets for compound series 8 and 9.Article Citation - WoS: 22Citation - Scopus: 22Synthesis and Anticancer Activity Evaluation of New Isoindole Analogues(Birkhauser Verlag, 2017) Köse, Aytekin; Bal, Yıldız; Şanlı Mohamed, Gülşah; Kara, YunusWe have developed a versatile synthetic approach for the synthesis of new isoindole derivatives via the cleavage of ethers from tricyclic imide skeleton compounds. An exo-cycloadduct prepared from the Diels–Alder reaction of furan and maleic anhydride furnished imide derivatives. The epoxide ring was opened with Ac2O in the presence of a catalytic amount of H2SO4 in order to yield new isoindole derivatives (8a and 8b). The anticancer activity of these compounds was evaluated against MCF-7 (breast adenocarcinoma) and A549 (adenocarcinomic human alveolar basal epithelial) cell lines. The synthesized compounds showed concentration- and time-dependent inhibitory effects on the viability of both cell lines. Compound 8a was more toxic compared to 8b in both cancer cell lines, having higher cytotoxicity against A549 cells. Testing the toxicity properties of these compounds on the BEAS 2B (human bronchial epithelial) cell line indicated that while both compounds decreased the cell viability of cancer cells, they were less toxic on healthy lung cells. Microscopy images of A549 cells after treatment with the new isoindole derivatives displayed characteristic apoptotic morphology compared to BEAS 2B cells. The results demonstrated here suggest that these new compounds might be considered as possible potential anticancer agents for the treatment of lung and breast cancer. © 2017, Springer Science+Business Media New York.