Journal of Molecular Recognition最新文献

{"title":"Structure-based improvement of the binding affinity and recognition specificity of peptide competitors to target pediatric IL-5R/IL-5 interaction by gluing halogen bonds at their complex interface","authors":"Peipei Chu,&nbsp;Yeping Sheng,&nbsp;Chentao Shen,&nbsp;Yalin Xia,&nbsp;Lingjun Kong,&nbsp;Jiefan Sun","doi":"10.1002/jmr.3070","DOIUrl":"10.1002/jmr.3070","url":null,"abstract":"<p>Human interleukin-5 (IL-5) cytokine mediates the development of eosinophils and is involved in a variety of immune inflammatory responses that play a major role in the pathogenesis of childhood asthma, leukemia, and other pediatric allergic diseases. The immunomodulatory cytokine functions by binding to its cognate cell surface receptor IL-5R in a sheet-by-sheet manner, which can be conformationally mimicked and competitively disrupted by a double-stranded cyclic AF18748 peptide. In this study, we systematically examined the co-crystallized complex structure of human IL-5R with AF18748 peptide and rationally designed a halogen bond to glue at the protein–peptide complex interface by substituting the indole moiety of AF18748 Trp13 residue with a halogen atom (X = F, Cl, Br, or I). High-level theoretical calculations imparted presence of the halogen bond between the oxygen atom (O) of IL-5R Glu58 backbone and the halogen atom (<span></span>X) of AF18748 Trp13 side chain. Experimental assays confirmed that the halogen bond can promote peptide binding moderately or considerably. More importantly, the halogen bond not only enhances peptide affinity to IL-5R, but also improves peptide selectivity for its cognate IL-5R over other noncognate IL-R proteins. As might be expected, the affinity and selectivity conferred by halogen bond increase consistently in the order: H &lt; F &lt; Cl &lt; Br &lt; I. Structural modeling revealed that the halogen bond plus its vicinal π–cation–π stacking co-define a ringed noncovalent system at the complex interface, which involves a synergistic effect to effectively improve the peptide binding potency and recognition specificity.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"37 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138291199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the riddle of amine oxidase flavoenzyme reactivity on the stereoisomers of N-methyl-dopa and N-methyl-tyrosine","authors":"Oriol Gracia Carmona,&nbsp;Majd Lahham,&nbsp;Peter Poliak,&nbsp;Dominic Goj,&nbsp;Eva Frießer,&nbsp;Silvia Wallner,&nbsp;Peter Macheroux,&nbsp;Chris Oostenbrink","doi":"10.1002/jmr.3068","DOIUrl":"10.1002/jmr.3068","url":null,"abstract":"<p>Enzymes are usually stereospecific against chiral substrates, which is commonly accepted for the amine oxidase family of enzymes as well. However, the FsqB (fumisoquin biosynthesis gene B) enzyme that belongs to the family of sarcosine oxidase and oxidizes L-<i>N</i>-methyl-amino acids, shows surprising activity for both enantiomers of <i>N</i>-methyl-dopa. The aim of this study is to understand the mechanism behind this behavior. Primary docking experiments showed that tyrosine and aspartate residues (121 and 315 respectively) are located on the ceiling of the active site of FsqB and may play a role in fixing the <i>N</i>-methyl-dopa via its catechol moiety and allowing both stereoisomers of this substrate to be in close proximity of the N5 atom of the isoalloxazine ring of the cofactor. Three experimental approaches were used to prove this hypothesis which are: (1) studying the oxidative ability of the variants Y121F and D315A on <i>N</i>-methyl-dopa substrates in comparison with <i>N</i>-methyl-tyrosine substrates; (2) studying the FsqB WT and variants catalyzed biotransformation via high-performance liquid chromatography (HPLC); (3) molecular dynamics simulations to characterize the underlying mechanisms of the molecular recognition. First, we found that the chemical characteristics of the catechol moiety of <i>N</i>-methyl-dopa are important to explain the differences between <i>N</i>-methyl-dopa and <i>N</i>-methyl-tyrosine. Furthermore, we found that Y121 and D315 are specific in FsqB and not found in the model enzyme sarcosine oxidase. The on-bench and theoretical mutagenesis studies show that Y121 residue has a major role in fixing the <i>N</i>-methyl-dopa substrates close to the N5 atom of the isoalloxazine ring of the cofactor. Simultaneously, D315 has a supportive role in this mechanism. Jointly, the experimental and theoretical approaches help to solve the riddle of FsqB amine oxidase substrate specificity.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"37 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmr.3068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134649208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of mitogen-activated protein kinase 7 inhibitors from natural products: Combined virtual screening and dynamic simulation studies","authors":"Bandar Alharbi,&nbsp;Lina I. Alnajjar,&nbsp;Hassan H. Alhassan,&nbsp;Shama Khan,&nbsp;Talha Jawaid,&nbsp;Bekhzod S. Abdullaev,&nbsp;Nawaf Alshammari,&nbsp;Dharmendra Kumar Yadav,&nbsp;Mohd Adnan,&nbsp;Anas Shamsi","doi":"10.1002/jmr.3067","DOIUrl":"10.1002/jmr.3067","url":null,"abstract":"<p>Mitogen-activated protein kinase 7 (MAPK7) is a serine/threonine protein kinase that belongs to the MAPK family and plays a vital role in various cellular processes such as cell proliferation, differentiation, gene transcription, apoptosis, metabolism, and cell survival. The elevated expression of MAPK7 has been associated with the onset and progression of multiple aggressive tumors in humans, underscoring the potential of targeting MAPK7 pathways in therapeutic research. This pursuit holds promise for the advancement of anticancer drug development by developing potential MAPK7 inhibitors. To look for potential MAPK7 inhibitors, we exploited structure-based virtual screening of natural products from the ZINC database. First, the Lipinski rule of five criteria was used to filter a large library of ~90,000 natural compounds, followed by ADMET and pan-assay interference compounds (PAINS) filters. Then, top hits were chosen based on their strong binding affinity as determined by molecular docking. Further, interaction analysis was performed to find effective and specific compounds that can precisely bind to the binding pocket of MAPK7. Consequently, two compounds, ZINC12296700 and ZINC02123081, exhibited significant binding affinity and demonstrated excellent drug-like properties. All-atom molecular dynamics simulations for 200 ns confirmed the stability of MAPK7-ZINC12296700 and MAPK7-ZINC02123081 docked complexes. According to the molecular mechanics Poisson–Boltzmann surface area investigation, the binding affinities of both complexes were considerable. Overall, the result suggests that ZINC12296700 and ZINC02123081 might be used as promising leads to develop novel MAPK7 inhibitors. Since these compounds would interfere with the kinase activity of MAPK7, therefore, may be implemented to control cell growth and proliferation in cancer after required validations.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92154790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The metabolic fingerprint of chronic hepatitis C progression: Metabolome shifts and cutting-edge diagnostic options","authors":"Amar Deep,&nbsp;Suchit Swaroop,&nbsp;Durgesh Dubey,&nbsp;Atul Rawat,&nbsp;Ajay Verma,&nbsp;Bikash Baisya,&nbsp;Rashmi Parihar,&nbsp;Amit Goel,&nbsp;Sumit Rungta","doi":"10.1002/jmr.3066","DOIUrl":"10.1002/jmr.3066","url":null,"abstract":"<p>Hepatitis C virus infection causes chronic diseases such as cirrhosis and hepatocellular carcinoma. Metabolomics research has been shown to be linked to pathophysiologic pathways in liver illnesses. The aim of this study was to investigate the serum metabolic profile of patients with chronic hepatitis C (CHC) infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Nuclear magnetic resonance (NMR) was used to evaluate the sera of 83 patients with CHC virus and 52 healthy control volunteers (NMR). Then, multivariate statistical analysis was used to find distinguishing metabolites between the two groups. Sixteen out of 40 metabolites including include 3-HB, betaine, carnitine, creatinine, fucose, glutamine, glycerol, isopropanol, lysine, mannose, methanol, methionine, ornithine, proline, serine, and valine—were shown to be significantly different between the CHC and normal control (NC) groups (variable importance in projection &gt;1 and <i>p</i> &lt; 0.05). All the metabolic perturbations in this disease are associated with pathways of Glycine, serine, and threonine metabolism, glycerolipid metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, alanine, aspartate, and glutamate metabolism. Multivariate statistical analysis constructed using these expressed metabolites showed CHC patients can be discriminated from NCs with high sensitivity (90%) and specificity (99%). The metabolomics approach may expand the diagnostic armamentarium for patients with CHC while contributing to a comprehensive understanding of disease mechanisms.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71424350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A brief account of evolution of assays to study carbohydrate—protein interaction","authors":"Suhas Ballal","doi":"10.1002/jmr.3065","DOIUrl":"10.1002/jmr.3065","url":null,"abstract":"<p>Molecular recognition remains one of the most desirable means of cellular communication. Each cell offers a unique surface pattern of biomolecules that makes it very specific about the nature of molecules that interact with the cell. Protein–glycan interaction has been one of the most common forms of cell signaling. Glycans expressed on the cell surface interact with an exogenous protein, and in many cases lead to a physiological response. These carbohydrate-binding proteins, commonly known as lectins, are very specific to the glycan they bind to. An exogenous lectin interacting with an animal cell surface glycan is generally studied using the classical hemagglutination assay. However, this method presents certain challenges that make it imperative to design and develop novel methods that are more specific and efficient in their interaction. In the last decade, a few methods have been developed to analyze more diverse reactions and use a lesser amount of sample. In some cases, the processing of the sample is also reduced. This review discusses how the methods have evolved over the decades and how they have reduced error while becoming more efficient.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49678538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-enzymatic glycation and aggregation of camel immunoglobulins induce breast cancer cell proliferation","authors":"Nouf O. Alafaleq,&nbsp;Ghaida I. Alruwaished,&nbsp;Mohd Shahnawaz Khan,&nbsp;Samia T. Al-Shouli,&nbsp;Ahmed H. Mujamammi,&nbsp;Essa M. Sabi,&nbsp;Khalid M. Sumaily,&nbsp;Mohammed Almansour,&nbsp;Majed S. Alokail","doi":"10.1002/jmr.3062","DOIUrl":"10.1002/jmr.3062","url":null,"abstract":"<p>Glycation of biomolecules results in the formation of advanced glycation end products (AGEs). Immunoglobulin G (IgG) has been implicated in the progression of various diseases, including diabetes and cancer. This study purified three IgG subclasses (IgG1, IgG2, and IgG3) from <i>Camelus dromedarius</i> colostrum using ammonium sulfate fractionation and chromatographic procedures. SDS-PAGE was performed to confirm the purity and molecular weight of the IgG subclasses. Several biochemical and biophysical techniques were employed to study the effect of glycation on camel IgG using methylglyoxal (MGO), a dicarbonyl sugar. Early glycation measurement showed an increase in the fructosamine content by ~four-fold in IgG2, ~two-fold in IgG3, and a slight rise in IgG1. AGEs were observed in all classes of IgGs with maximum hyperchromicity (96.6%) in IgG2. Furthermore, glycation-induced oxidation of IgGs led to an increase in carbonyl content and loss of -SH groups. Among subclass, IgG2 showed the highest (39.7%) increase in carbonyl content accompanied by 82.5% decrease in -SH groups. Far UV-CD analysis illustrated perturbation of β-sheet structure during glycation reaction with MGO. Moreover, glycation of IgG proceeds to various conformational states like aggregation and increased hydrophobicity. In addition, the cytotoxicity assay (MTT) illustrated the proliferation of breast cancer cells (MCF-7) with IgG2 treatment.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 12","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbonic anhydrase inhibition by antiviral drugs in vitro and in silico","authors":"Cüneyt Türkeş","doi":"10.1002/jmr.3063","DOIUrl":"10.1002/jmr.3063","url":null,"abstract":"<p>Enzyme inhibition is a commonly utilized method for controlling enzymatic activity in various physiologically relevant biological systems. Herein, the selected five active antiviral drugs, abacavir, emtricitabine, lamivudine, ribavirin, and ritonavir, were assayed as inhibitors of two human isoforms of the metalloenzyme carbonic anhydrase (<i>h</i>CA, EC 4.2.1.1) involved in various physiological/pathological conditions. For this aim, in vitro and in silico studies were performed to gain insights into the plausible binding interactions and affinities for the antiviral drugs within <i>h</i>CA I and II isoforms' active sites. The <i>h</i>CA I, an isoform involved in some pathological conditions such as retinal or cerebral edema, was moderately inhibited by these five drugs at micromolar concentrations with <i>K</i>_Is spanning from 0.49 ± 0.05 to 3.51 ± 0.37 μM compared with the reference drug acetazolamide (AAZ, <i>K</i>_I of 0.19 ± 0.01 μM). Moreover, <i>h</i>CA II, a promising target for edema, glaucoma, epilepsy, and altitude sickness, was a reasonably inhibited isoform by these agents, with <i>K</i>_Is in the range of 0.64 ± 0.08–5.80 ± 0.64 μM compared with AAZ (<i>K</i>_I of 0.17 ± 0.01 μM). Both in vitro and in silico results demonstrated significant interactions between these five drugs and <i>h</i>CAs and that they can support therapeutic targets against the above-mentioned pathological conditions. Additionally, the results obtained will help optimize the clinical dosage regimens of these drugs and avoid drug–drug interactions unexpectedly when used in combination with other agents.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 12","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41128523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the molecular role of MUC5B in progressive lung adenocarcinoma: Prospects for early diagnosis","authors":"Gayathri Ashok,&nbsp;Abirami Soundararajan,&nbsp;Anand Anbarasu,&nbsp;Sudha Ramaiah","doi":"10.1002/jmr.3064","DOIUrl":"10.1002/jmr.3064","url":null,"abstract":"<p>Gel-forming mucin MUC5B is significantly deregulated in lung adenocarcinoma (LUAD), however, its role in tumor progression is not yet clearly understood. Here, we used an integrated computational-pipeline-initiated with gene expression analysis followed by network, functional-enrichment, O-linked glycosylation analyses, mutational profiling, and immune cell infiltration estimation to functionally characterize MUC5B gene in LUAD. Thereafter, clinical biomarker validation was supported by the overall survival (OA) and comparative expression profiling across clinical stages using computational algorithms. The gene expression profile of LUAD identified MUC5B to be significantly up-regulated (logFC: 2.36; <i>p</i>-value: 0.01). Network analysis on LUAD interactome screened MUC5B-related genes, having key enrichment in immune suppression and O-linked glycosylation with serine–threonine-rich tandem repeats being highly glycosylated. Furthermore, positive correlation of mutant MUC5B with immune cells in tumor microenvironment (TME) such as cancer-associated fibroblasts and myeloid-derived suppressor cells indicates TME-mediated tumor progression. The positive correlation with immune inhibitors suggested the enhanced tumor proliferation mediated by MUC5B. Structural stability due to genetic alterations identified overall rigid N–H-backbone dynamics (S²: 0.756), indicating an overall stable mutant protein. Moreover, the low median OA (&lt;50 months) with a hazard ratio of 1.4 and clinical profile of MUC5B gene showed high median expression corresponding to lymph node (N2) and tumor (T3) stages. Our study concludes by highlighting the functional role of O-glycosylated and mutant MUC5B in promoting LUAD by immune suppression. Further, clinical gene expression validation of MUC5B suggests its potential role as a diagnostic biomarker for LUAD metastasis.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41147506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of α-glucosidase and α-amylase inhibitory effects of phenoxy chalcones and molecular modeling studies","authors":"Bedriye Seda Kurşun-Aktar,&nbsp;Şevki Adem,&nbsp;Gizem Tatar-Yilmaz,&nbsp;Zeyad Adıl Hameed Hameed,&nbsp;Emine Elçin Oruç-Emre","doi":"10.1002/jmr.3061","DOIUrl":"10.1002/jmr.3061","url":null,"abstract":"<p>Diabetes mellitus is one of the most critical health problems affecting the quality of life of people worldwide, especially in developing countries. According to the World Health Organization reports, the number of patients with diabetes is approximately 420 million, and this number is estimated to be 642 million in 2040. There are 2 main types of diabetes: Type 1 (T1DM), where the body cannot produce enough insulin, and Type 2 (T2DM), where the body cannot use insulin properly. Patients with T1DM are treated with insulin injections while oral glucose-lowering drugs are used for patients with T2DM. Oral antihyperglycemic drugs used in the treatment of type 2 diabetes mellitus have different mechanisms. Among these, α-Glucosidase and α-amylase inhibitors are one of the most important inhibitors. The antidiabetic effect of the chalcones, which show rich activity, draws attention. This research aims to synthesize chalcone derivatives that could show potential antidiabetic activity. In this study, the inhibitory activity of the chalcone compounds (<b>4a</b>-<b>4g, 5a-5g</b>) was tested against α-glucosidase and α-amylase enzymes. Besides, molecular modeling was utilized to predict potential interactions of the synthesized compounds that exhibit inhibitory effects. In both in vitro and in silico studies, the analyses revealed that compound <b>5e</b> exhibits strong inhibitory effects against α-glucosidase enzymes (Binding energy: −7.75 kcal/mol, IC₅₀: 28.88 μM). Additionally, compound <b>4f</b> demonstrates encouraging inhibitory effects against α-Amylase (Binding energy: −11.08 kcal/mol, IC₅₀: 46. 21 μM).</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, biological activities, and evaluation of molecular docking-dynamics studies of new thiosemicarbazones that may be effective against Alzheimer's disease","authors":"Neslihan Conger,&nbsp;Derya Osmaniye,&nbsp;Begüm Nurpelin Sağlık,&nbsp;Serkan Levent,&nbsp;Yusuf Ozkay,&nbsp;Zafer Asım Kaplancıklı","doi":"10.1002/jmr.3059","DOIUrl":"10.1002/jmr.3059","url":null,"abstract":"<p>Donepezil is one of the most used drugs in the treatment of Alzheimer's disease. Its activity as an AChE inhibitor makes new studies with these enzyme inhibitors attractive. For this purpose, in this study, 12 compounds including thiosemicarbazone pharmacophore, have been synthesized for the treatment of the Alzheimer's disease. 3,4-Dimethoxybenzene or 1,3-benzodioxolone rings were used for the PAS region. The substituted piperazine benzene structure is preferred for the CAS region. At the same time, the thiosemicarbazone pharmacophore structure with known ChE enzyme inhibition potential was used as a bridge connecting the CAS and PAS regions. Structure determination of compounds <b>3a–3l</b> were revealed using ¹³C-NMR, ¹H-NMR, and HRMS spectroscopic methods. The inhibition profile of obtained compounds (<b>3a–3l</b>) against ChE was evaluated using in vitro modified Ellman method. Compounds <b>3a</b>, <b>3b</b>, <b>3f</b>, <b>3g</b> and <b>3i</b> exhibited inhibitory activity against the AChE enzyme. Compound <b>3a</b> showed the highest inhibitory potential with an IC₅₀ = 0.030 ± 0.001 μM. As a result of molecular docking studies, compound <b>3a</b> displayed important interactions compared to other active derivatives. Molecular dynamics studies are important to see the stability of the complex formed by ligand and protein. RMSD, RMSF ang Rg parameters were calculated via dynamic studies. In conclusion, compound <b>3a</b> may be a potential AChE enzyme inhibitor with its strong inhibitory potential and behavior in silico.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 12","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10312585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}