Koprulu, Cigdem; Faydali, Nagihan; Muhammed, Muhammed Tilahun; Dilek, Esra; Kucukoglu, Kaan; Sirinzade, Hanif

This study analyzes the inhibitory effects of newly synthesized compounds of the K1–12 series on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes comparatively using IC50 and Kᵢ parameters. Initially, a series of novel 5-fluoroindolylmethylene hydrazone derivatives (K1–12) were designed and synthesized. The structures of the synthesized compounds were elucidated using 1H and 13C NMR spectroscopy as well as mass spectrometric analyses. Subsequently, their inhibitory effects on AChE and BChE were evaluated in vitro . Molecular docking studies performed for all compounds with AChE and BChE enzymes, and pi interactions and conventional hydrogen bonds were involved in protein-ligand interactions. The molecular dynamics (MD) simulation study of the compound with the highest binding potential to the AChE and BChE structures, K10, disclosed that the complexes obtained from docking would be stable. Moreover, the compound is predicted to have a greater tendency to remain within the binding site of the BChE structure. The density functional theory (DFT) study resulted in similar levels of chemical stability and reactivity for the relatively active compounds. The findings revealed that, especially, the K5 and K10 compounds exhibited higher inhibitory activity than donepezil against BChE and AChE, respectively. The results indicate that these compounds could be potential agents for the treatment of neurodegenerative diseases in the future.

Yavuz, Sevtap Caglar; Emul, Zeynep; Icer, Fatih; Yavuz, Emre; Ozdokur, Volkan Kemal; Cirak, Burcu Bozkurt

This paper targets to synthesize a nano-composite with high photocatalytic performance and research the possibility of utilizing it for dye and drug removal from wastewater. Herein, ZnBi2O4/Ag2WO4 nanocomposite photocatalyst was successfully synthesized via two step hydrothermal/precipitation method. The photocatalytic activity of the synthesized nanocomposite was evaluated by its effect on the degradation of methylene blue dye and sulfamerazine drug under UV light. The results revealed that the ZnBi2O4/Ag2WO4 nanocomposite achieved a significantly higher photocatalytic efficiency (96% degradation of methylene blue in 1 h) compared to ZnBi2O4 (41%) and Ag2WO4 (76%) within only 60 min. The exceptional photocatalytic degradation efficiency of the ZnBi2O4/Ag2WO4 nanocomposite against methylene blue and sulfamerazine can be attributed to the effects of reduced charge carrier recombination resulting from the synergistic effect of surface adsorption-photocatalytic degradation interaction of ZnBi2O4 and Ag2WO4.

Türkmenoğlu, Burçin; Bayar, İrem; Kökbudak, Zülbiye; Akkoc, Senem

The pyrimidine nucleus is a vital pharmacophore that exhibits excellent pharmacological activity. A Schiff base containing a pyrimidine nucleus was obtained in two steps. This compound was assessed on the human prostate (PC3) and liver (HepG2) cancer cell lines using the MTT method. The prepared compound 3 was determined to have a high cytotoxic effect towards prostate cancer with an IC50 value of 9.32 μM. Since experimental prostate and liver cancer studies were examined, the molecular docking study's target structures were determined accordingly. In molecular docking studies, compound 3 interacted in silico with the crystal structure of the human HER2 kinase domain (PDB Id: 3PP0), the crystal structure of VEGFR-2 (PDB Id: 4ASD), and the crystal structure of EGFR tyrosine kinase (PDB Id: 4HJO), respectively. As a result of these interactions, binding energy values were calculated, and binding modes were determined. Additional in vitro and in vivo experiments targeting other cancer cell lines will provide deeper insight into the anticancer spectrum of this compound and new studies on this compound will be planned in the following years. Furthermore, optimizing and studying such pyrimidine-based Schiff base compounds for improved selectivity and potency against prostate cancer is also considered to be valuable as it may increase the potential to capture potential drug candidates.

Çağlar Yavuz, Sevtap

This study focused on the structural/electronic features of an anti-ulcer agent, gefarnate. The molecular geometry of the compound was calculated using Gaussian 09 W software and the structure was optimized using the DFT/B3LYP method with the 6–31++G(d,p) basis set ground state. Also, in silico studies like molecular docking studies and ADME/T estimation were carried out using web-based tools and software. The protein used in these calculations is the crystal structure of the 3U6J, VEGFR2 kinase domain in complex with a pyrazolone inhibitor. The binding energy for the gefarnate molecule-VEGFR2 kinase complex has been computed as −8.6 kcal/mol. The compound showed no toxicity properties including cytotoxic, mutagenic, carcinogenic, or immunogenic.

Türkmenoğlu, Burçin

Before the experimental studies of a compound to be synthesized from in vitro to in vivo, it is possible to save both time and money with in silico approaches only with Computer Aided Drug Design (CADD) methods. In other words, compounds that can be new drug candidates can be suggested by drug design using computational drug discovery strategies. In this study, all molecules in the ChEMBL Database were virtual screened based on drugs with inhibitory properties on the Epidermal Growth Factor Receptor (EGFR), one of the receptor tyrosine kinases, which is effective in cancer cells. During this High-Throughput Screening (HTS), the number of compounds was minimized according to the parameters of the reference drugs, physicochemical properties such as logP, M.W., HBA, HDB, RosLip. As a result of in silico approaches and molecular docking analysis, ten compounds with the highest docking scores were determined and a model compound that could be a new drug candidate was proposed.