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The incidence of neurodegenerative Alzheimer's and Parkinson's diseases is increasing worldwide every day, and treatment options are currently very limited. There is no definitive cure for these diseases, and the drugs available in clinical practice only provide symptomatic relief without halting the progression of neurodegeneration. One commonly employed strategy in the treatment of Alzheimer's and Parkinson's diseases is to return neurotransmitter levels by inhibiting enzymes like cholinesterase (ChE) and monoamine oxidase (MAO). In this research, we focused on investigating the therapeutic potential of 2-[2-(substituted benzylidene)hydrazinyl]-4-(substituted phenyl)thiazole derivatives (2a–2h) by incorporating hydrazine, known for its inhibitory effects on monoamine oxidases, into the structure of molecules that inhibit acetylcholinesterase. Thiazole ring was included in these derivatives due to its reported inhibitory activity against both cholinesterases and monoamine oxidase enzymes. When the enzyme inhibition activities were evaluated, it was determined that compounds 2c, 2d, and 2h showed the highest inhibitory activity against AChE, while compounds 2f and 2h expressed the highest activity against MAO-B. It was determined that compound 2h had the highest inhibitory activity on both AChE (0.030 ± 0.001 μM) and MAO-B (0.048 ± 0.002 μM) and compound 2h was the only compound with conspicuous dual inhibitory activity. Furthermore, molecular docking calculations and molecular dynamics simulations were found to agree with experimental results. [ABSTRACT FROM AUTHOR]

In this study, the synthesis of N‐(5,6‐methylenedioxybenzothiazole‐2‐yl)‐2‐[(substituted)thio/piperazine]acetamide/propanamide derivatives (3a‐3k) and to investigate their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β‐secretase 1 (BACE‐1) inhibition activity were aimed. Mass, 1H NMR, and 13C NMR spectra were utilized to determine the structure of the synthesized compounds. Compounds 3b, 3c, 3f, and 3j showed AChE inhibitory activity which compound 3c (IC50 = 0.030 ± 0.001 µM) showed AChE inhibitory activity as high as the reference drug donepezil (IC50 = 0.0201 ± 0.0010 µM). Conversely, none of the compounds showed BChE activity. Compounds 3c and 3j showed the highest BACE‐1 inhibitory activity and IC50 value was found as 0.119 ± 0.004 µM for compound 3j whereas IC50 value was 0.110 ± 0.005 µM for donepezil, which is one of the reference substance. Molecular docking studies have been carried out using the data retrieved from the server of the Protein Data Bank (PDBID: 4EY7 and 2ZJM). Using in silico approach behavior active compounds (3c and 3j) and their binding modes clarified. [ABSTRACT FROM AUTHOR]

AbstractNew choline esterase inhibitors and B-secretase inhibitors present promising treatment options for the treatment of Alzheimer's disease (AD). In this study, molecular docking was performed using our chemistry library to discover lead compounds. Molecular docking was employed to predict binding affinities, while molecular dynamics (MD) simulations provided insights into the stability of the ligand–enzyme interactions. To improve the activity, 12 new derivatives were designed and synthesized based on the lead compound obtained. The structures of the synthesized compounds were identified by 1H-NMR,13C-NMR, and HRMS techniques. Their activities on choline esterase enzymes and Beta-secretase 1 enzyme were elucidated through in vitro studies. Compound 4f had an IC50 = 0.026 ± 0.001 µ. value against the acetylcholinesterase (AChE) enzyme and an IC50 = 0.125 ± 0.005 µ. value against the BACE-1 enzyme. The excellent activity of compound 4f was supported by molecular docking and MD simulation studies. [ABSTRACT FROM AUTHOR]

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The study aimed to investigate 12 novel thiazole compounds in the treatment of neurodegenerative disorders. The compounds produced were evaluated for their inhibitory efficacy against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidases (MAOs). Among the compounds, 5d , 5e , and 5j showed the highest AChE inhibitory activity. The IC 50 values for compounds are 0.223 ± 0.010 µM, 0.092 ± 0.003 µM, and 0.054 ± 0.002 µM, respectively. In addition, molecular docking analyses and molecular dynamic simulation were used to examine the interactions of these compounds with protein sites. The results suggest that thiazole-ring compounds could serve as a promising basis for the development of drugs aimed at treating neurodegenerative diseases (NDD), caused by Parkinson's and Alzheimer's diseases.

Sorafenib, a multiple kinase inhibitor, is widely used as a first-line treatment for hepatocellular carcinoma. However, there is a need for more effective alternatives when sorafenib proves insufficient. In this study, we aimed to design a structure that surpasses sorafenib's efficacy, leading us to synthesize sorafenib-ruthenium complexes for the first time and investigate their properties. Our results indicate that the sorafenib-ruthenium complexes exhibit superior epidermal growth factor receptor (EGFR) inhibition compared to sorafenib alone. Interestingly, among these complexes, Ru3S demonstrated high activity against various cancer cell lines including sorafenib-resistant HepG2 cells while exhibiting significantly lower cytotoxicity than sorafenib in healthy cell lines. Further evaluation of cell cycle, cell apoptosis, and antiangiogenic effects, molecular docking, and molecular dynamics studies revealed that Ru3S holds great potential as a drug candidate. Additionally, when free Ru3S was encapsulated into polymeric micelles M1 , enhanced cytotoxicity on HepG2 cells was observed. Collectively, these findings position Ru3S as a promising candidate for EGFR inhibition and warrant further exploration for drug development purposes.