Sürdürülebilir Kalkınma Amaçları
Yayınlar
- MakaleAçık Erişim2026Scopus SJRQ2Tamoxifen-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.
- MakaleYalnız künye2026Scopus SJRQ2Synthesis, biological evaluation, and computational analysis of chromone-based carboxamides targeting Alzheimer’s disease
Kilic, Burcu; Aksakal, Fatma; Dogruer, Deniz S.
Alzheimer's disease (AD) is among the most serious long-term health problems of the last few decades. Regrettably, the current lack of treatment options for AD has made it a highly sought-after topic of drug development research. The utilization of multitarget directed ligand design (MTDL) has been the primary focus of research on developing pharmaceuticals for AD. By this approach, we designed novel cholinesterase inhibitors (ChEI) that may also exhibit additional monoamine oxidase (MAO) inhibitory, antioxidant, and metal chelator properties. Within the scope of the current work, twenty N-(2-(tertiaryamine-substituted)ethyl)-4-oxo-4H-chromene-2/3-carboxamide derivatives were synthesized and characterized. Subsequently, we conducted biological investigations for enzyme inhibitory (ChEs and MAO), antioxidant, and metal-chelating activities. Furthermore, we assessed the in silico physicochemical parameters of the compounds to evaluate their drug-likeness or druggability. Additionally, comprehensive computational studies were conducted, including density functional theory (DFT)-based frontier molecular orbital (FMO) analysis, global chemical reactivity descriptors, and molecular electrostatic potential (MEP) surface analysis, along with molecular docking, to elucidate the electronic properties, reactive sites, and binding interactions of the compounds with ChE enzymes.
- MakaleYalnız künye2024Scopus SJRQ3A fully conjugated imidazole-fused perylene phenantroline ruthenium(II) complex in photocatalytic oxidation
Aksakal, Nuray Esra; Aksakal, Fatma; Gül, Elif Yıldız; Eçik, Esra Tanrıverdi; Yuksel, Fatma
In this investigation, the suitability of a specially designed imidazole-fused perylene ruthenium(II) molecule, denoted as Ru-PhP, was explored by employing the photooxidation of 1,5-dihydroxynaphthalene (DHN) to produce Juglone as a model reaction. This distinctive, entirely conjugated compound was synthesized through the reaction between perylene imide anhydride dye (1) and a ruthenium(II) phenanthroline complex (2) in the presence of a Zn(OAc)2 catalyst. Structural analyses of the compound were performed by using general spectroscopic methods including FT-IR, 1H NMR, 13C- NMR, and MALDI-TOF analyses. Various photophysical properties, including the UV–Vis absorption spectrum, fluorescence emission spectrum, and fluorescence quantum yield, were examined. The photochemical studies via indirect method endorsed Ru-PhP as an efficient photosensitizer. Furthermore, Ru-PhP proved to be highly effective in facilitating the photooxidation of DHN to yield juglone. DFT-based natural bond orbital analysis revealed intramolecular charge transfer in Ru(II) coordination environment, with a strong total stabilization energy (25.31 eV) between the ruthenium acceptor and nitrogen donors in the bipyridine and phenanthroline units. The dispersion of HOMO electrons within the imidazole-bridged perylene moiety and the localization of LUMO electrons near Ru(II)-coordinated bipyridine units were observed through Frontier Molecular Orbital and molecular electrostatic potential analyses. Ru-PhP is proposed as photocatalyst for photo redox catalytic organic reactions.
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İncele - MakaleYalnız künye2024Scopus SJRQ2Multifunctional anti-Alzheimer's agents: Synthesis, biological evaluation, and molecular docking study of new 2-phenoxyacetamide/3-phenoxypropanamide/4-oxobutanamide derivatives
Shakila, Shakila; Kilic, Burcu; Bardakkaya, Merve; Aksakal, Fatma; Sagkan, Rahsan Ilikci; Dogruer, Deniz S.
In the current study, three series of new compounds were designed and synthesized through hit optimization, based on the hit compound with a structure (E)-N-(4-{[benzyl(methyl)amino]methyl}thiazol-2-yl)-3-(3,4-dimethoxyphenyl)prop‑2-enamide, which was found as a potential multifunctional anti-Alzheimer agent in our previous study. Then, the biological activities of synthesized compounds (4a-c, 13a-b and 15a-c) were evaluated. The results indicated that 4b, a 2-phenoxyacetamide derivative, exhibited good multifunctional activities. Namely, compound 4b displayed better BChE inhibition (BChE IC50 = 2.10 µM) and antioxidant activity (ORAC = 1.18 Trolox equivalents) compared to the hit compound (BChE IC50 = 14.70 µM, ORAC = 0.5 Trolox equivalents). Additionally, 4b was able to chelate all tested biometals and it also exhibited a neuroprotective effect (63 %), comparable to reference ferulic acid (77 %) while maintaining its safety upon PC12 cell line. When it comes to lowering the levels of TNF-α, NO, IL-1β, and IL-6, 4b performed better activity, relative to the other synthesized compounds. Subsequently, in silico studies such as physicochemical properties, density functional theory (DFT) computational approach and molecular docking studies were performed.
AtıfScopus2WoS2OpenAlex3İncele - MakaleAçık Erişim2023Antitüberküloz triptantrin analoglarının elektronik ve topolojik özelliklerinin ve enoil-acp redüktaz ile etkileşimlerinin in siliko yöntemlerle incelenmesi
Aksakal, Fatma
Amaç: Bu çalışmanın amacı, bir dizi triptantrin analogunun yapı- antitüberküloz aktivite ilişkilerini ve bu analogların Mycobacterium tuberculosis enoyl-acyl taşıyıcı protein (enoyl- ACP) redüktaz (InhA) ile bağlanma mekanizmalarını incelemektir. Yöntem: İlk olarak, elektronik-topolojik yöntem (ETM) ile bileşiklerin yapısındaki farmakofor ve anti-farmakoforlar tespit edilmiş ve ETM-Sinir Ağları (Neural Networks, NN) yaklaşımına dayalı olarak aktivite tahmin modelleri geliştirilmiştir. İkinci aşamada, moleküler kenetlenme yöntemi kullanılarak bileşiklerin InhA enzimine bağlanma afiniteleri ve konformasyonları elde edilmiş; bağlanmada etkili olan kovalent olmayan etkileşimler incelenmiştir. Son aşamada, bu etkileşimler sınır moleküler orbitallerin (FMO) elektron yoğunluğu dağılımı üzerinden tartışılmıştır. Bulgular: İnceleme altındaki bileşik serileri üzerine ETM-NN yönteminin uygulaması sonucunda Mycobacterium tuberculosis H37Rv suşuna karşı aktivite gösteren bileşiklerin karakteristik farmakofor ve anti-farmakofor özellik gösteren moleküler fragmanları tespit edilmiştir. Aktivite tahmin sistemine giren beş farmakofor (Phi) ve beş anti-farmakoforun (APhi) istatistiksel özellikleri sırasıyla 0,90 ve 0,86 olarak elde edilmiştir. Moleküler kenetlenme ve elektron yoğunluğu dağılımı analizleri, aktif bileşiklerin InhA enzimine daha kuvveti bağlandığını ortaya koymuştur. Sonuç: Tespit edilen farmakofor gruplar, kenetlenme sonuçları ve elektronik yapı hesaplamalarına dayalı olarak, Mycobacterium tuberculosis H37Rv'nin antitüberküloz aktivitesi için bir prognoz modeli geliştirilmiştir. Bu prognoz modeli, yeni potansiyel antitüberküloz ilaçların tasarımında kullanılabilecektir.
- MakaleAçık Erişim2023Scopus SJRQ2Synthesis 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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İncele - MakaleYalnız künye2023Scopus SJRQ1New thiourea and benzamide derivatives of 2-aminothiazole as multi-target agents against Alzheimer's disease: Design, synthesis, and biological evaluation
Kilic, Burcu; Bardakkaya, Merve; Ilıkcı Sagkan, Rahsan; Aksakal, Fatma; Shakila, Shakila; Dogruer, Deniz S.
In this study, two series of compounds were designed and synthesized, bearing thiourea and benzamide derivatives at position 2 of 4-subtituted-2-aminothiazole, respectively. Then, the inhibition potency of all final compounds for cholinesterase enzymes were evaluated. Among the thiourea derivatives, 3c (IC50 = 0.33 μM) was identified as the most potent and selective butyrylcholinesterase inhibitor. Additionally, benzamide derivative 10e (AChE IC50 = 1.47 and BChE IC50 = 11.40 μM) was found as a dual cholinesterase inhibitor. The type of inhibition for both compounds was determined by kinetic studies and the results showed that the compounds were mixed type inhibitors. Moreover, all title compounds were investigated in terms of their antioxidant (DPHH, ORAC) and metal chelator activities. In addition, the neuroprotective effects of selected compounds (3c, 3e, 6c, 6e and 10e) against H2O2-induced damage in the PC12 cell line were tested. The experimental findings demonstrated that thiourea-derived 6e (40.4 %) and benzamide-derived 10e (37.8 %) have a neuroprotective effect of about half as ferulic acid at 10 μM. Subsequently, the cytotoxicity of selected compounds was examined by the MTT assay, and the compounds were found not to have cytotoxic effect on the PC12 cell line in 24 h. Additionally, compounds 6e and 10e were also found to be more effective in inhibiting the release of IL-1β, IL-6, TNF-α and NO compared to other selected compounds in this study.
AtıfScopus39WoS32OpenAlex39İncele
