Tok, Fatih; Dumani, Alessia; Güney, Sultan; Abas, Burçin İrem; Kozan, Bensu; Türkeş, Cüneyt; Duran, Hatice Esra; Başoğlu, Faika; Çevik, Özge; Ece, Abdulilah

In aqueous media, enzyme–ligand recognition is shaped not only by direct contacts but also by solvent-mediated interaction networks that persist across time scales. Here, cholinesterases (AChE and BChE) and cytosolic human carbonic anhydrases ( h CA I and h CA II) were investigated as two disease-relevant enzyme systems in solution, and twelve thiourea–pyrimidine benzenesulfonamide derivatives were synthesized and structurally characterized. Enzyme inhibition was quantified by steady-state kinetics; inhibition constants ( K I) were obtained by nonlinear global fitting of untransformed rate data, with Lineweaver–Burk plots used only for visualization. To connect solution-phase inhibition with molecular recognition, docking was validated by redocking (heavy-atom RMSD <2.0 Å across targets), and representative complexes were examined by 500 ns explicit-solvent MD simulations (TIP3P, 0.15 M NaCl, NPT), revealing stable binding modes and persistent, frequently water-mediated interaction patterns consistent with experimental trends. Cellular relevance was assessed in MKN-28 gastric cancer cells with L929 fibroblasts as a non-malignant control. Compounds with improved cytotoxic selectivity toward MKN-28 were identified, and the lead compound ( 11 ) was further evaluated by Annexin V/PI flow cytometry, showing a shift from viable cells toward apoptotic populations under the tested conditions. In silico ADMET profiling suggested moderate lipophilicity across the series, while highlighting elevated polar surface area and compound-dependent toxicity flags as parameters to monitor during optimization. Overall, thiourea–pyrimidine benzenesulfonamides emerge as multifunctional modulators of ChEs and cytosolic h CAs within the applied biochemical and cellular assays.

Güleç, Özcan; Türkeş, Cüneyt; Arslan, Mustafa; Demir, Yeliz; Dincer, Busra; Ece, Abdulilah; Küfrevioğlu, Ömer İrfan; Beydemir, Şükrü

In the present medical epoch, the prevailing approach of drug discovery, which focuses on inhibiting a single target, has been superseded by the concept of designing drugs that target more than one specific site. Herein, we present the design and synthesis of a novel series of 1-oxo-3,4-dihydronaphthalene substituted sulfonamides (5a-j) with human carbonic anhydrase (hCA) and acetylcholinesterase (AChE) inhibitory activities as potential dual-target agents. The design of target compounds 5a-j incorporated two key elements: i) The sulfonamide group, which is widely recognized for its high affinity for the active site of hCAs, and ii) the effectiveness of 2-benzylidene-1-tetralone class compounds in some neurodegenerative disorders. All reported sulfonamides were evaluated for their inhibitory effect against hCA I, II isoforms, and AChE. Both hCAs, and AChE were potently inhibited by 5a-j with KI constants in the nanomolar range; 47.71–113.20 nM, 28.05–206.60 nM, and 87.38–136.60 nM, respectively, compared to standard inhibitors, acetazolamide (KIs of 439.17 and 98.28 nM for hCA I and hCA II, respectively) and tacrine (KI of 159.61 nM). 5i exhibited the best multi-target inhibitory activity against hCA I (KI of 47.71 nM), hCA II (KI of 30.75 nM), and AChE (KI of 88.97 nM), while 5b showed a selectivity index (hCA I/II) of 3.61. Moreover, a cytotoxic activity assay for sulfonamides 5a-j was applied on the human breast adenocarcinoma MCF-7 cell line as well as on the non-tumoral mouse fibroblast L929 cell. Thereafter, extensive molecular dynamics simulations revealed the dynamic behavior of ligand/enzyme complex and predicted vital ligand contacts in the binding pocket.

Beytur, Murat; Kardaş, Faruk; Akyıldırım, Onur; Özkan, Abdullah; Bankoğlu, Bahar; Yüksek, Haydar; Yola, Mehmet Lütfi; Atar, Necip

Ceftizoxime (CFX) is used to reduce the infection caused by both gram-negative and gram-positive bacteria. In this report, silver@gold nanoparticles (Ag@AuNPs) involved in 5-(5-bromo-2-hydroxybenzylidenamino)-2-mercaptobenzimidazole (ILs) was firstly synthesized. After that, CFX imprinted glassy carbon electrode (GCE) was prepared. The formation of the surfaces was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), electrochemical impedance spectroscopy (EIS) and x-ray photoelectron spectroscopy (XPS). CFX imprinted electrochemical surface was formed in the presence of 100.0 mM phenol containing 25.0 mM CFX as template. The linearity range and the detection limit (LOD) of the developed nanosensor were calculated as 1.0 × 10− 9 - 1.0 × 10− 11 M and 2.0 × 10− 12 M, respectively.

Akyıldırım, Onur; Kardaş, Faruk; Beytur, Murat; Yüksek, Haydar; Atar, Necip; Yola, Mehmet Lütfi

Citrinin (CIT) is mutagenic and resistant to decomposition. In addition, it is founded in many foods and causes the significant diseases in human body. In this report, an imprinted electrochemical surface based on glassy carbon electrode (GCE) modified with palladium nanoparticles (PdNPs) involved in 5-(4-Hydroxybenzylidenamino)-2-mercaptobenzimidazole (BZ) functionalized graphene quantum dots (GQDs) was formed for CIT analysis. The formation of the surfaces was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS). CIT imprinted electrochemical surface was formed in the presence of 80.0 mM pyrrole as monomer and 20.0 mM CIT as template. The linearity range and the detection limit (LOD) of the developed nanosensorwere calculated as 1.0 × 10− 9–5.0 × 10− 9 M and 2.0 × 10− 10 M, respectively.

Kardaş, Faruk; Beytur, Murat; Akyıldırım, Onur; Yüksek, Haydar; Yola, Mehmet Lütfi; Atar, Necip

In the present report, a new voltammetric sensor based on copper oxide nanoparticles involved in 2-(3-acetoxy-4-methoxybenzylidenamino)-thiophenol (AMT) ionic liquid (CuO NPs/ILs) was developed for atrazine (ATR) analysis. Firstly, the CuO NPs/ILs modified surface was investigated by using transmission electron microscopy (TEM), X-ray diffraction (XRD), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and energy dispersive X-ray analysis (EDX). The linearity range and the detection limit (LOD) of the prepared sensor were calculated as 1.0 × 10− 11–2.0 × 10− 9 and 2.0 × 10− 12 M, respectively. Voltammetric sensor was also applied to wastewater samples with high recovery.