Şerife Gökçe Çalışkan

Background/Objectives: Breast cancer remains a leading cause of cancer-related mortality among women, highlighting the need for further investigation of bioactive compounds with selective effects on cancer cells. This study evaluated the biological effects of the natural coumarin derivative umbelliferone in MCF-7 breast cancer cells using integrated in silico and in vitro approaches. Methods: Molecular docking predicted interactions with AKT1, mTOR, PI3Kα, and Caspase-7, while molecular dynamics simulations and MM/PBSA calculations provided further information on interactions with AKT1 and mTOR. Results: Umbelliferone reduced MCF-7 cell viability in a concentration-dependent manner, with an IC₅₀ of 492 µM after 24 h, whereas 50% viability was not reached in BJ normal fibroblasts up to 1400 µM, corresponding to an IC₅₀ > 1400 µM and a selectivity index > 2.85. Annexin V-FITC/PI analysis showed increased apoptotic populations, with total apoptosis significantly increased at 800 µM. Colony formation analysis further indicated reduced clonogenic capacity. At 400 µM, umbelliferone significantly increased relative Caspase-3/7 and Caspase-9 activities to 1.873 ± 0.635 and 2.483 ± 0.092, respectively, whereas neither activity was significantly increased at 800 µM. In silico ADME analysis predicted properties compatible with commonly used drug-likeness criteria. Conclusions: Collectively, the findings demonstrate effects of umbelliferone on cell viability, apoptosis, clonogenic capacity, and caspase activity in MCF-7 cells, with comparatively lower cytotoxicity toward normal fibroblasts. Computational findings remain hypothesis-generating and do not establish direct target engagement or pathway inhibition. Further mechanistic and in vivo studies are required to determine the biological and pharmacological relevance of these findings.

Phytochemicals, particularly pentacyclic triterpenes, have garnered attention for their multi-targeted anticancer potential. Ursolic acid (UA), an ursane-type triterpene, exhibits anticancer activity in various tumor types; however, its selective effects on osteosarcoma remain unexplored. This study investigated the anti-proliferative and anti-migratory effects of UA on Saos-2 human osteosarcoma cells. Cell viability and proliferation were evaluated using CCK-8 and colony formation assays, migration was assessed via a wound healing assay, apoptosis was examined through mitochondrial membrane potential (MMP) analysis, and molecular interactions were explored using in silico molecular docking and dynamics simulations.UA significantly reduced cell viability (IC₅₀: 39.48 µg/mL) and exhibited a favorable selectivity index (SI: 4.87), indicating preferential activity against cancer cells. UA also inhibited colony formation and migration and induced apoptosis, as evidenced by the reduced mitochondrial membrane potential. Molecular docking revealed strong binding affinities of UA to AKT1 and mTOR, and molecular dynamics simulations confirmed stable protein–ligand interactions. These results suggest that UA may exert anticancer effects, at least in part, by modulating the AKT/mTOR signaling pathway.Overall, this study provides mechanistic insights into UA’s selective activity of UA against osteosarcoma cells and supports its potential as a lead bioactive compound. Further in vivo and mechanistic studies are warranted to clarify the therapeutic relevance of these findings.

It is aimed to perform an evaluation of a hydrazone derivative of the vic-dioxime ligand by examining its structural properties, bioactivity via molecular docking and absorption, distribution, metabolism, excretion (ADME) analysis, and stability using molecular dynamics (MD). With this respect, the innovative design, synthesis, and advanced in silico analysis of a novel vic-dioxime hydrazone ligand, (1Z,2E)-2-(hydroxyimino)-N'-[(1Z)-3,4,5-trimethoxyphenyl)methylene]ethanehydroximohydrazide (LH2) was explored. The compound was characterized through a series of spectroscopic techniques, including ¹H NMR, ¹³C NMR, FT-IR, and UV-Vis spectroscopy. In silico studies were performed to evaluate the ligand's binding affinities to major proteins of RAS/RAF/MEK/ERK signaling pathway through molecular docking. ADME profiling was conducted to assess the ligand's pharmacokinetic properties. Additionally, MD analysis was performed to evaluate the binding stability of the target-compound complex through RMSD, RMSF, RG, hydrogen bonding and MMPBSA free energy calculations. As a result of molecular docking analysis, the compound was found to have the highest binding energy value to RAS among the other target proteins RAF and ERK. In addition, it was obtained that LH2 complies with the conditions required to satisfy Lipinski's rule of five. Moreover, ERK-ligand complex exhibited the highest stability among the tested targets according to the MD simulation results. According to the results of the investigation, in silico anti-cancer activity was revealed based on molecular docking analysis and it was determined that novel vic-dioxime hydrazone ligand could act as a targeted therapeutic RAS/RAF/MEK/ERK pathway inhibitor in colorectal cancer.

It is aimed to investigate the effects of the vic-dioxime compound and Zn(II) complex bearing the hydrazone group on breast cancer and various receptor tyrosine kinases (RTKs) by molecular docking method and to investigate their structures in terms of bioactivity and quantum chemistry. vic-dioxime compound carrying hydrazone group and its Zn(II) complex were synthesized. Density functional theory method was used for determining the structures of the molecules in terms of quantum chemical calculations and for analysing the molecular electrostatic potential and frontier molecular orbitals. For in silico investigation, molecular docking analysis was performed to analyse the inhibitory effects of the compounds against EGFR, VEGFR-2 and IGFR RTKs and ADME bioactivity properties were evaluated. The molecular docking results revealed that especially Zn(II) complex has a high binding affinity against RTKs. Both of the compounds’ drug similarity properties conformed the Lipinski’s rule of five. Zn(II) complex has the highest ionization energy and ω value which corresponds to have higher capacity of electron donation and a great electrophilicity, respectively. In light of the results of this study, it is suggested that compounds based on the hydrazone group carrying vic-dioxime can be used as powerful compounds in new anti-breast cancer drug design studies.

In this study, we synthesized and characterized a novel unsymmetrical meso-aryl substituted porphyrin derivative. Comprehensive structural elucidation was achieved using a suite of spectroscopic techniques, including 1H and 13C Nuclear Magnetic Resonance (NMR), Fourier-Transform Infrared (FT-IR) spectroscopy, and Ultraviolet-Visible (UV-Vis) spectroscopy. To further investigate the compound's potential therapeutic applications, in silico studies were performed, focusing on its interactions with breast cancer-associated target receptors, specifically the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor (IGFR), through molecular docking simulations. Additionally, bioactivity properties were evaluated via absorption, distribution, metabolism, and excretion (ADME) analysis. Complementary to the experimental work, Density Functional Theory (DFT) calculations at the B3LYP/6-311G+(d,p) level were conducted to optimize the molecular structure and determine key quantum chemical parameters, such as the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) distributions. These computational insights provide a deeper understanding of the electronic characteristics and reactivity of the synthesized compound, highlighting its potential for further development as a cancer therapeutic agent.

The use of beverages containing caffeine has increased significantly in recent years due to their stimulant effects. The aim of this study was to determine the possible adverse effects of caffeine and taurine on young adults’ cardiovascular systems using linear and nonlinear parameters for this analysis. This study was carried out with 56 students from Aydın Adnan Menderes University. The participants were divided into four main groups: caffeine, taurine, caffeine + taurine, and a control. Blood pressure and electrocardiogram measurements were performed before the ingredients were consumed. After 30 and 60 min, the measurements were repeated. Linear and nonlinear analyses were performed on the heart rate variability data 60 min after consumption. Compared with taurine and the combination of caffeine + taurine, caffeine was found to have the most adverse effects on the hemodynamic parameters and the linear and nonlinear parameters of heart rate variability in the young adult participants. It was also found that the presence of taurine may have repressed the adverse effects of caffeine.

Background: Cancer is one of the diseases affecting a large population worldwide and resulting in death. Finding new anti-cancer drugs that are target-focused and have low toxicity is of great importance. Objective: This study aimed to investigate the effects of vic-dioxime derivatives carrying hydrazone group and its Zn(II) complex on cancer using molecular docking, bioactivity and quantum chemical calculations. Methods: Molecular docking studies were performed on epidermal growth factor receptor and vascular endothelial growth factor receptor 2 target proteins. Furthermore, molecular geometry was performed, and the frontier molecular orbitals, Mulliken charges and molecular electron density distribution were evaluated using density functional theory. Also, the bioactivity parameters of the compounds were evaluated, and ADME analysis was performed using web-based tools. Results: Higher binding affinity was observed for Zn(II) complex with target proteins vascular endothelial growth factor receptor 2 and against epidermal growth factor receptor when compared with LH2. Only the Zn(II) complex against the epidermal growth factor receptor had ligand efficiency and fit quality in the valid range. Furthermore, LH2 has the most potent electrophilic ability (acceptor) among other compounds. Moreover, both LH2 and Zn(II) complexes strongly satisfy Lipinski’s rule of five. Conclusion: In conclusion, these novel compounds, especially Zn(II) complex, can be new candidates for anticancer drug development studies which are target-focused and have low toxicity.

With the effect of developing technology, humanity is constantly exposed to more electromagnetic fields. Regional studies are gaining importance for determining the possible problems. In this study, extremely low-frequency electromagnetic field (ELF-EMF) measurements were carried out in Aydın Adnan Menderes University Central Campus in areas where university students are frequently found, at 25 randomly selected points, in the region where high voltage lines pass and around transformers, and to evaluate the awareness of university students about the ELF-EMF they are exposed to. For this purpose, the necessary magnetic field and electric field strength measurements were made and a questionnaire was applied to determine the awareness level of the students. Results were evaluated by comparing them with the ICNIRP limit values. Accordingly, it has been concluded that Aydın Adnan Menderes University Central Campus can be accepted as a relatively safe area since electromagnetic field exposure values are within the ICNIRP safe limit values. In addition, as a result of the questionnaire, it was determined that the young people were conscious to a certain extent about ELF-EMF, but they did not pay attention to protect themselves against the possible effects of ELF-EMF. It is important to make the necessary initiatives in order to raise awareness of young people on this issue.

Molecular docking process was performed to investigate the interactions between the synthesized compounds and human epidermal growth factor protein kinase domain EGFR (PDB ID:1M17) and cyclin-dependent kinase-2 CDK2 (PDB ID:3IG7) proteins. HOMO LUMO orbital energy analysis, quantum chemical calculations were made and the bioactivity parameters of the compounds were evaluated. NiII and CuII complexes of the L1H2 L2H2 and L3H2, ligands showed higher binding affinity to EGFR and CDK2. Especially, [Cu(L1H)2] and [Cu(L2H)2] complexes can be suggested as hit compounds against CDK2 and EGFR, respectively. These were supported by the inhibition constant values which were the lowest when compared to others. L1H2 L2H2 and L3H2, ligands had the lowest binding energy values when compared to metal complexes. Also, [Cu(L2H)2] complex had a high binding energy value against EGFR. [Ni(L2H)2] and [Cu(L2H)2] complexes with EGFR had the highest LE and FQ values and these were found to be in the recommended range. Furthermore, [Cu(L3H)2] had an acceptable FQ value however its LE value was out of range. Besides, [Cu(L2H)2] had a potent and sufficient electrophile ability (acceptor) among other compounds. In conclusion, these compounds may be suitable compounds for further analysis in anti-cancer drug development with low toxic and targeted properties.