Sürdürülebilir Kalkınma Amaçları

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• MakaleAçık Erişim2026Scopus SJRQ2/r/kostu/10654
  Tamoxifen-Based Dimers: Design, Synthesis, Cell Viability Evaluation on Breast Cancer Cells, and Computational Insights

  Ertugrul, Berrak; Aytatli, Abdulmelik; Karatas, Omer Faruk; Essiz, Selcuk; Aksakal, Fatma; Saracoglu, Nurullah

  Tamoxifen (TMX) resistance presents a significant challenge in the treatment of ER+ breast cancer. In this study, four novel tamoxifen-based dimers were synthesized and evaluated for their antitumor activities. Among these, (Z,Z)-1 exhibited potent antiproliferative effects in ER+ cells, demonstrating selective toxicity toward cancer cells over normal cells. (Z,Z)-1 significantly outperformed tamoxifen with IC50 values of 9.18 μM (24 h) and 6.86 μM (48 h) against MCF-7 cells. Additionally, it showed greater selectivity toward ER+ breast cancer cells compared with both triple-negative cancer cells and non-cancerous cells. Mechanistic studies indicated that (Z,Z)-1 induces apoptosis in MCF-7 cells through a cell-cycle-independent mechanism, unlike TMX, which arrests cells at the G0/G1 phase. These findings suggest that (Z,Z)-1 may be a promising candidate for further development as an alternative to tamoxifen therapy in ER+ breast cancer treatment. The docking studies revealed that (Z,Z)-1 exhibits the strong binding affinity to ERα, highlighting its potential as a promising therapeutic candidate for ER+ breast cancer treatment.

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• MakaleAçık Erişim2023Scopus SJRQ2/r/kostu/10725
  Synthesis and evaluation of multitarget new 2-aminothiazole derivatives as potential anti-Alzheimer's agents

  Bardakkaya, Merve; Kilic, Burcu; Sagkan, Rahsan Ilıkcı; Aksakal, Fatma; Shakila, Shakila; Dogruer, Deniz S.

  In this study, two diverse series of 2-aminothiazole-based multitarget compounds, one propenamide and the other propanamide derivatives, were designed and synthesized. Subsequently, their anticholinesterease and antioxidant (ORAC) activities were tested. Among them, compound 3e was the most potent acetylcholinesterase (AChE) inhibitor (AChE IC50 = 0.5 μM, butyrylcholinesterase [BChE] IC50 = 14.7 μM) and compound 9e was the most potent BChE inhibitor (AChE IC50 = 3.13 μM, BChE IC50 = 0.9 μM). Kinetic experiments showed that both compounds were mixed-type inhibitors. According to the anticholinesterease activity results, five compounds (3e, 4e, 5e, 9d, and 9e) were selected for further activity studies, all of which are dual cholinesterase inhibitors. Then, selected compounds were investigated in terms of their metal chelation activity. Moreover, their neuroprotective effects against H2O2-induced damage in the PC12 cell line were evaluated at 10 μM and the results showed that the neuroprotective effect of 3e was 53% compared with the reference ferulic acid (77%). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results of selected compounds revealed that the compounds were noncytotoxic. Additionally, 3e was more effective in reducing lipopolysaccharides-induced interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and nitric oxide (NO) production in the human monocyte derived from patient with acute monocytic leukemia cell line compared with other selected compounds. Finally, a molecular docking study was also performed.

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  AtıfScopus27·WoS24·OpenAlex28

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