WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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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.
