Browsing by Author "Beydemir Ş."

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A novel series of thiosemicarbazone hybrid scaffolds: Design, synthesis, DFT studies, metabolic enzyme inhibition properties, and molecular docking calculations
(2023-05-15) Yakan H.; Muğlu H.; Türkeş C.; Demir Y.; Erdoğan M.; Çavuş M.S.; Beydemir Ş.
The fourteen new thiosemicarbazone derivatives of Schiff base were synthesized from the condensation reactions of two different aldehydes (3‑hydroxy-4-methoxhybenzaldehyde and 3-ethoxhy-4-hydroxybenzaldehyde) with various substituted-thiosemicarbazides. Structures of the compounds (1-14) were characterized by using FT-IR, 1H NMR, and 13C NMR spectroscopic techniques, and elemental analysis. Furthermore, the enzyme inhibitory effect of the obtained hybrid scaffolds was studied. They exhibited highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (KI values are in the range of 111.00 ± 12.12 to 381.60 ± 38.10 nM, 120.60 ± 20.45 to 338.90 ± 42.18 nM, and 100.60 ± 11.31 to 285.30 ± 45.27 nM for AChE, hCA I, and hCA II, respectively). DFT analyzes were performed to demonstrate the usability of some electronic parameters and nucleophilic-electrophilic attack abilities of the compounds in predicting enzyme inhibition properties. A correlation was seen between the HOMO energy eigenvalues of the compounds and the inhibition reactivity, and revealing that QTAIM calculations could also be used to predict the probability of electrophilic and nucleophilic attacks. Findings supporting that hCA I and AChE enzyme inhibition reactions primarily proceed through electrophilic attack, while hCA II reactions tend to occur via nucleophilic attack have been obtained. Also, molecular docking studies were conducted to confirm the outcomes of studies on binding affinities and the most powerful derivatives. The obtained results showed that the novel thiosemicarbazone derivatives may lead to the development of novel types of pharmacological agents in the treatment of patients with Alzheimer's disease, idiopathic intracranial hypertension, glaucoma, and related conditions.
Enzyme inhibition, molecular docking, and density functional theory studies of new thiosemicarbazones incorporating the 4-hydroxy-3,5-dimethoxy benzaldehyde motif
(2022-01-01) Demir Y.; Türkeş C.; Çavuş M.S.; Erdoğan M.; Muğlu H.; Yakan H.; Beydemir Ş.
New Schiff base-bearing thiosemicarbazones (1–13) were obtained from 4-hydroxy-3,5-dimethoxy benzaldehyde and various isocyanates. The structures of the synthesized molecules were elucidated in detail. Density functional theory calculations were also performed to determine the spectroscopic properties of the compounds. Moreover, the enzyme inhibition activities of these compounds were investigated. They showed highly potent inhibition effects on acetylcholinesterase (AChE) and human carbonic anhydrases (hCAs) (KI values are in the range of 51.11 ± 6.01 to 278.10 ± 40.55 nM, 60.32 ± 9.78 to 300.00 ± 77.41 nM, and 64.21 ± 9.99 to 307.70 ± 61.35 nM for AChE, hCA I, and hCA II, respectively). In addition, molecular docking studies were performed, confirmed by binding affinities studies of the most potent derivatives.
Novel asymmetric biscarbothioamides as Alzheimer's disease associated cholinesterase inhibitors: synthesis, biological activity, and molecular docking studies
(2024-06-03) Muğlu H.; Yakan H.; Erdoğan M.; Topal F.; Topal M.; Türkeş C.; Beydemir Ş.