In this study, a series of N‐substituted‐(p‐tolyl)pyridazin‐3(2H)‐one derivatives were synthesized and evaluated for their AChE inhibitory activity. The chemical structures of novel compounds 5(a–m) were confirmed by 1H‐NMR, 13C‐NMR, IR and HRMS analysis. In order to eliminate the symptomatic effects of Alzheimer's disease, the proposed compounds were evaluated by acetylcholinesterase inhibition activity study in accordance with the cholinergic hypothesis. The results revealed that the N‐substituted‐(p‐tolyl)pyridazin‐3(2H)‐one derivatives inhibited the enzymes significantly. Ki values for acetylcholinesterase in the range of 0.56±0.15–4.12±1.42 μM. Compound 5 h demonstrated the greatest in AChE activity compared with tacrine (0.56±0.15 μM). Molecular docking studies were performed for all compounds that compared tacrine in AChE activity in‐vitro. As a result of molecular docking studies (ΔGBind, docking score, XP Gscore, Glide energy, Glide emodel), 5 f, 5 g and 5 h compounds showed good inhibitory properties in the AChE active site as in silico.

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A series of novel (p-chlorophenyl)-3(2H)pyridazinone compounds were synthesized starting from p-chloroacetophenone as AChE/BChE inhibitors. The chemical structures of all the compounds were identified by spectral analysis. Cholinesterase inhibition activity studies and in silico studies of compounds designed to eliminate the symptomatic effects of Alzheimer's disease and slow down neurodegeneration were evaluated. According to the results obtained, it was revealed that Nsubstituted-(p-chlorophenyl)pyridazin-3(2H)-one derivatives inhibited enzymes significantly. K i values were found for acetylcholinesterase in the range of 10.2 � 4.0-20.9 � 7.6 nM and for butyrylcholinesterase in the range of 0.70 � 0.34-1.67 � 1.12 nM. Compound 5e showed the best effect on AChE activity compared to Tacrine. Also, compound 5b showed the best effect in BChE inhibition. The interactions of the synthesized compounds with the best experimental activities against AChE, BChE, respectively, were investigated by in silico approaches. In molecular docking, 5b compound with AChE crystal structure (PDB ID:1ACJ), binding site and binding parameters of 5e compound with BChE crystal structure were investigated in detail. The results indicated that compound 5b and 5e could be a promising lead compound for further development as a therapeutic agent for Alzheimer's disease.

Alzheimer hastalığı (AH), demansın en yaygın nedeni olan kronik nörodejeneratif bir hastalıktır. Hastalığa yakalanma riski yaşla birlikte artar. Hastalığın histopatolojisi incelendiğinde senil amiloid plakları, nörofibriler yumak oluşumu, sinaps-nöron kaybı ve beyinde belirgin atrofi saptanır. Alzheimer hastalığında asetilkolin sentezinden sorumlu olan kolin asetil transferaz düzeyindeki azalma %58-90'dır. Mevcut ilaçlar hastalığın ilerlemesini durduramadığından, hastalığın temel nedenini hedef alan yeni ilaçlara büyük ihtiyaç vardır. Bu çalışmada asetilkolinesteraz inhibisyonu gösteren triazol-piridazinon türevi bileşikler sentezlenmiştir ve enzim inhibisyonları araştırılmıştır. Bileşik 6e, 0.049 ± 0.014 µM Ki değeri ile en güçlü inhibitör etkiyi göstermiştir (Takrin Ki= 0.226 ± 0.025 µM). Ayrıca sentezlenen tüm bileşikler için in-silico çalışmalar yapıldı.

Antibiotic resistance is one of the most serious global problems around the world. Pseudomonas aeruginosa is gram-negative bacteria and plays important role in local and systemic infections. In our work, we tried to understand mode of antimicrobial action of ferroccene-boronic acid over Pseudomonas aeruginosa via metabolomics and proteomics analysis. In proteomics analysis, we found that ferrocene-boronic acid effects various antimicrobial targets like ATP-dependent DNA helicase RecQ, Transcription-repair-coupling factor and Primasome assembly protein PriA. In metabolomics analysis, the ferrocene-boronic acid induced various metabolites involved in pyrimidine metabolism, lipid and fatty acid metabolism. Moreover, various polyamines like spermine and spermidine, which are very important for antibiotic resistance, pathogenesis and bacterial biofilm formation were decreased by ferroceneboronic acid. We believe that our results will contribute further studies regarding organometallic compounds in microbiology filelds.

Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible, biodegradable polymer approved by the FDA and EMA, which is the most widely used in the field of health. In this study, PLGA was synthesized primarily from lactide and glycolide by polycondensation and ring-opening polymerization. Then, amino acid derivatives of PLGA were synthesized by the reaction of PLGA and amino acids in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The polymers synthesized were PLGA, PLGA-L-glutamic acid (PLGA-G), and PLGA-L-aspartic acid (PLGA-A). The chemical structure of these polymers was confirmed by 1H and 13C Nuclear Magnetic Resonance (1H NMR and 13C NMR), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Gel Permeation Chromatography (GPC). When the 13C NMR analyses of PLGA-amino acid derivatives were observed, an increase in the number of carbonyl carbons around 170 ppm was found and the structure accuracy was supported. In addition, when the FTIR analyses of PLGA-amino acid derivatives were examined, the structure was confirmed by observing the signal of the amide bond carbonyl vibration at 1700 cm-1. While the typical endothermic thermogram of the PLGA-amino acid derivative structures was observed by DSC analysis, it was shown that the structures were low molecular weight polymers [~5000-6000 Da] by GPC analysis.

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