Biotechnology and applied biochemistry最新文献

{"title":"Enhanced Thermal Stabilization of Yeast d-Aspartate Oxidase Through Intersubunit Disulfide Bond Engineering","authors":"Sota Zaitsu,&nbsp;Daiki Imanishi,&nbsp;Narito Ogata,&nbsp;Shouji Takahashi","doi":"10.1002/bab.70163","DOIUrl":"10.1002/bab.70163","url":null,"abstract":"<div>\u0000 \u0000 <p>The flavoenzyme <span>d</span>-aspartate oxidase (DDO) is a promising candidate for several biotechnological applications, including the detection of acidic <span>d</span>-amino acids and the optical resolution of their racemic mixtures. The DDO from the yeast <i>Cryptococcus humicola</i> strain UJ1 (ChDDO) exhibits high catalytic activity and strict substrate specificity toward <span>d</span>-Asp; however, its practical use is hindered by limited stability, particularly upon dilution. In this study, we engineered ChDDO by introducing an intersubunit disulfide bond through structure-guided substitutions (G87C/Y292C). The resulting variant exhibited improved resistance to heat-induced loss of activity in residual-activity assays after defined heat treatments, while retaining comparable apparent <i>K</i>_m and <i>k</i>_cat values for <span>d</span>-Asp. In a residual-activity assay using the purified enzymes, the apparent (operational) <i>T</i>₅₀ increased by 21.8°C compared with the wild-type enzyme. Biochemical analyses confirmed the formation of an intersubunit disulfide bond and suggest that it contributes to improved resistance to heat-induced loss of activity under the tested conditions, without compromising the enzyme's useful catalytic properties. Collectively, these results indicate that intersubunit disulfide engineering can improve the functional robustness of ChDDO under the assay conditions used, thereby supporting its practical use in DDO-based applications.</p>\u0000 </div>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":"73 5","pages":"2178-2188"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580546","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":"Multitarget Enzyme Inhibition and Anticancer Potential of 3-Substituted Indole Derivatives Supported by Molecular Docking Studies","authors":"Adnan Cetin,&nbsp;Ercan Oguz,&nbsp;Fikret Türkan,&nbsp;Karolina Babijczuk,&nbsp;Natalia Berdzik,&nbsp;Ceylan Kurgan,&nbsp;Beata Jasiewicz","doi":"10.1002/bab.70166","DOIUrl":"10.1002/bab.70166","url":null,"abstract":"<div>\u0000 \u0000 <p>The enzymes and anticancer properties of disubstituted indole, indole-imidazole, and indole-pyrazole derivatives were determined. These building blocks are based on a privileged 3-substituted indole scaffold that, in turn, has been used to explore potential effects for the enzymes and cancer cells. Inhibition studies for acetylcholinesterase (AChE), glutathione <i>S</i>-transferase (GST), alpha-amylase (α-Amy), and alpha-glucosidase (α-Gly) were conducted. IC₅₀ values for the 3-substituted indoles were identified as follows: AChE, 3.329 ± 0.975 to 5.544 ± 0.380 µM; GST, 2.228 ± 0.407 to 6.026 ± 1.100 µM; α-Gly, 3.380 ± 0.616 to 5.330 ± 1.024 µM; and α-Amy, 3.397 ± 0.472 to 5.173 ± 0.682 µM. Indole derivatives that exhibited strong enzyme inhibition were investigated for their cytotoxic effects on hepatocellular carcinoma (HepG2) and glioblastoma (U-87) cell lines at 24 and 48 h. Overall, it was found that some indole derivatives showed IC₅₀ values comparable to those of the standard drug, and throughout the process, some indole derivatives exhibited good IC₅₀ values, indicating good activity and low cytotoxic effects. The most active compounds were identified as compound 15 against GST (IC₅₀ = 2.228 ± 0.407 µM), compounds 1 and 16 against AChE (IC₅₀ = 3.329 ± 0.975 and 3.349 ± 0.845 µM), compounds 4 and 14 in HepG2 cells (IC₅₀ = 33.13 and 36.71 µM at 48 h), and compounds 12 and 17 in U-87 cells (IC₅₀ = 38.43 and 47.53 µM at 48 h). These indole-based derivatives are also subjected to a structure–activity relationship (SAR) study by the molecular docking method. Most indole derivatives showed enzyme inhibition results similar to, but below, those of the standard drug.</p>\u0000 </div>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":"73 5","pages":"2210-2222"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590286","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":"Immunoinformatics-Based Design of a Multi-Epitope Vaccine Targeting a Conserved Copper–Associated Protein in Neisseria gonorrhoeae","authors":"Sinethemba H. Yakobi,&nbsp;Uchechukwu U. Nwodo","doi":"10.1002/bab.70179","DOIUrl":"10.1002/bab.70179","url":null,"abstract":"<p><i>Neisseria gonorrhoeae</i> poses an urgent public health challenge due to rapidly increasing antimicrobial resistance and the absence of an effective vaccine. Targeting conserved bacterial pathways involved in essential physiological processes may provide new opportunities for vaccine antigen discovery. In this study, we applied an immunoinformatics-based pipeline to explore a conserved copper–associated protein as a potential antigenic source for multi-epitope vaccine design. Analysis of 396 clinical genomes confirmed high assembly quality and identified a highly conserved hypothetical protein (AKOBGLPP_01618) through proteome-wide screening for metal-binding signatures. The candidate exhibited strong predicted antigenicity, high prevalence across isolates (99.5%), and no detectable homology with human proteins. In silico analyses suggested potential copper-binding features based on predicted metal-coordinating residues and conserved genomic context. Epitope mapping identified B-cell epitope–rich regions that were refined into conserved, surface-accessible peptides. Predicted cytotoxic and helper T-cell epitopes were filtered for immunogenicity, safety, and strain conservancy prior to inclusion in a multi-epitope construct containing a TLR4-targeting adjuvant and processing-optimized linkers. The resulting 155-amino-acid construct demonstrated favorable physicochemical characteristics, predicted solubility, and an estimated global population coverage of 74.84%. Docking analyses suggested a consistent interaction propensity with the TLR4/MD-2 complex across multiple predicted conformations. Although these findings provide preliminary computational support for the proposed construct, experimental validation will be required to confirm antigen function, immunogenicity, and receptor engagement. Collectively, this study identifies a conserved copper–associated protein as a potential antigen source and presents a computational framework for exploring vaccine candidates against <i>N. gonorrhoeae</i>.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":"73 5","pages":"2373-2387"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bab.70179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833856","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":"Utilization of Sunflower Stalk Waste in Microbial Biomass Production with Lactobacillus rhamnosus GG","authors":"Zeynep Banu Güler,&nbsp;Mesut Bilgi,&nbsp;Ayşegül Peksel","doi":"10.1002/bab.70165","DOIUrl":"10.1002/bab.70165","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, microbial biomass production was carried out using <i>Lactobacillus rhamnosus</i> GG (LGG), a probiotic bacterium, by utilizing sunflower stalks, an agricultural waste, as a carbon source. In the first stage, the optimal growth conditions for LGG were determined, and biomass production was conducted under these conditions. The growth parameters of LGG were optimized based on pH, temperature, carbon source, and incubation time. According to the findings, the highest growth and biomass production of LGG were achieved using glucose as a carbon source at 37°C, with pH 6 and an incubation period of 24 h. In the second stage, sunflower stalks were used as a carbon source in biomass production. After being sterilized, the sunflower stalks were ground. The sunflower stalk waste was added directly to the culture medium in its ground form and also processed using an ultrasound-assisted extraction method before being incorporated into the medium. The results indicated that the culture medium containing ultrasound-assisted extracted sunflower stalk waste served as a more effective carbon source, compared to glucose and lactose, which were used as carbon sources in optimization studies. By analyzing the growth rate of LGG on this substrate and its intracellular protein amount, sunflower stalks were demonstrated to be a suitable substrate for biomass production.</p>\u0000 </div>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":"73 5","pages":"2202-2209"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590202","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":"Immunogenicity, Pharmaceutics, and Properties of Recombinant Aspergillus flavus Uricase Modified by Citric Acid/Ethylenediamine Carbon Dots","authors":"Hai-Ling Li,&nbsp;Hong-Bin Jia,&nbsp;Jin-Long He,&nbsp;Xiu-Feng Gao,&nbsp;Yong-Sheng Li","doi":"10.1002/bab.70174","DOIUrl":"10.1002/bab.70174","url":null,"abstract":"<div>\u0000 \u0000 <p>Clinically, patients with gout are often treated with uricase (Uox)-based drugs. While these medications are effective, many patients suffer from immune rejection associated with their use. To reduce Uox's immunogenicity, it was modified with carbon dots synthesized from citric acid and ethylenediamine (CA/EDA-CDs), forming CA/EDA-Uox. The particle size, zeta potential, and main functional groups of CA/EDA-CDs and CA/EDA-Uox were characterized by transmission electron microscopy (TEM), FT-IR, and dynamic light scattering (DLS). CCK8 and flow cytometry were used to detect the survival rate of L02 cells treated with CA/EDA-CDs and CA/EDA-Uox, respectively. After treatment with 1% CA/EDA-Uox for 2 weeks, IgG and IgM titers in rats were detected by ELISA. The particle size of CA/EDA-CDs is mainly 5 nm, and zeta potential is distributed in −10.3 mV and 5.8 mV. The cell survival rate and the number of fluorescently labeled cells were the highest in 1% CA/EDA-CDs and 1% CA/EDA-Uox treatment groups, respectively. No antibody was detected in 1% CA/EDA-Uox treated rats. The contents of IL-2, 6, 10, and TNF-β in the blood of quails were significantly lower than those in Uox group (<i>p</i> &lt; 0.01). The cytotoxicity of 1% CA/EDA-CDs and 1% CA/EDA-Uox were the lowest; there were less antibodies produced by 1% CA/EDA-Uox in rats. CA/EDA-Uox exhibits satisfactory safety, low immunogenicity, and favorable pharmacological properties. It holds promise for progression to the clinical trials and eventual clinical application.</p>\u0000 </div>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":"73 5","pages":"2299-2315"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763156","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":"Preparation and Characterization of PVA–SA Hydrogel Immobilized β-Galactosidase With Improved Catalytic Properties","authors":"Doruk Akdoğan,&nbsp;Ayşegül Peksel","doi":"10.1002/bab.70177","DOIUrl":"10.1002/bab.70177","url":null,"abstract":"<div>\u0000 \u0000 <p>This study reports the immobilization of <i>Aspergillus oryzae</i> β-galactosidase in a polyvinyl alcohol–sodium alginate (PVA–SA) hydrogel and its performance compared with the free enzyme. Through immobilization, the optimum temperature shifted from 40°C to 60°C, with the immobilized enzyme retaining high activity and exhibiting improved resistance to heat-induced inactivation. Although maximum catalytic activity was observed at pH 5.0 for both free and immobilized forms, the immobilized enzyme sustained higher stability in near-neutral and slightly alkaline environments. Kinetic analysis revealed that the <i>K</i>_m value increased from 0.21 to 0.33 mM, indicating diffusion limitations, whereas the apparent <i>V</i>_max rose from 0.40 to 1.71 U/mg protein. Storage experiments demonstrated improved stability at 4°C, with about 60% of the initial activity retained after 8 weeks, whereas freezing at −20°C accelerated inactivation. The immobilized enzyme retained more than 80% of its catalytic performance after three consecutive uses and still preserved approximately 65% following the fourth cycle. Lactose hydrolysis experiments confirmed efficient and sustained performance, reaching 78% conversion after 180 min.</p>\u0000 </div>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":"73 5","pages":"2338-2348"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763159","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":"Optimization of Fermentation Conditions Using Design of Experiment (DoE) to Enhance the Production of Antigenic Capsular Polysaccharides From Streptococcus pneumoniae Serotype 18C for Pneumococcal Vaccine Development","authors":"Amol Dattatraya Mahajan,&nbsp;Pramod Maruti Jadhav,&nbsp;Avinash Rohidas Memane,&nbsp;Gautam Kumar Jha,&nbsp;Swapan Kumar Jana,&nbsp;Prasad Deepak Dandekar,&nbsp;Pranav Deepak Pathak","doi":"10.1002/bab.70158","DOIUrl":"10.1002/bab.70158","url":null,"abstract":"<div>\u0000 \u0000 <p>Pneumococcal pneumonia, caused by <i>Streptococcus pneumoniae</i>, has emerged as a global health threat, especially in children below 5 years of age and elderly population. <i>S. pneumoniae</i> remains a major global health threat which necessitates scalable and high-yield vaccine production. This study presents an innovative fermentation platform for <i>S. pneumoniae</i> (serotype 18C) by optimizing an already refined media composition using data-driven Design of Experiment (DoE) approach. Unlike conventional applications, Plackett–Burman design (PBD) was strategically employed beyond screening, identifying statistically significant parameters and the interaction between key factors of dextrose, MgSO₄, pH, and aeration. Results reveal that pH level of 7.1 significantly enhances the antigenic capsular polysaccharide yield. Further, ANOVA analysis confirmed a strong synergistic effect between dextrose and MgSO₄. In addition, the present study also finds that fermentation at lower level of aeration (0.2 vvm) favors the bacterial growth aligning with <i>S. pneumoniae</i>’s facultative anaerobic or microaerophilic nature. The downstream processing integrating centrifugation and diafiltration (100 kDa) improves the product recovery and purity reinforcing the process efficiency. The unconventional application of PBD combined with systematic optimization of refined process sets a new benchmark for pneumococcal fermentation strategies. The findings demonstrate that precise modulation of fermentation conditions can enhance the vaccine antigen yield addressing the scalability challenges in industrial production. Future work may focus on extending this DoE-based platform to other serotypes of <i>S. pneumoniae</i> and refining fermentation kinetics for next generation pneumococcal vaccine. This study not only challenges the traditional experimental set up, but paves the way for adaptive, data-driven bioprocess innovations in vaccine manufacturing.</p>\u0000 </div>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":"73 5","pages":"2123-2134"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502972","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":"Synergistic Enhancement of Antioxidant Activity in Arbutus unedo Leaf Extract by Biological Fluids: Implications for Functional and Nutraceutical Applications","authors":"Idir Moualek,&nbsp;Hamdi Bendif,&nbsp;Karima Benarab,&nbsp;Giulio Lupidi,&nbsp;Fehmi Boufahja,&nbsp;Stefania Garzoli,&nbsp;Karim Houali","doi":"10.1002/bab.70164","DOIUrl":"10.1002/bab.70164","url":null,"abstract":"<p>This study examined the effect of biological fluids (saliva, blood plasma, and urine) on the antioxidant capacity of an aqueous extract derived from <i>Arbutus unedo</i> leaves. The extract displayed a concentration-dependent reducing activity in the ferric reducing power assay (IC₅₀ = 292 ± 7.54 µg/mL) and phosphomolybdenum assays (IC₅₀ = 461.67 ± 4.16 µg/mL), indicating considerable antioxidant potential, albeit inferior to ascorbic acid (IC₅₀ = 56.72 ± 2.79 and 156.55 ± 7.40 µg/mL, respectively). The investigation via high-performance liquid chromatography-mass spectrometry (HPLC-MS) discovered significant phenolic substances, such as quinic acid, arbutin, epicatechin, and quercetin derivatives, which likely contribute to the reported effects. The interaction with biological fluids enhanced the antioxidant activity synergistically. Saliva (50 µL) enhanced molybdenum reduction by 10%, but plasma (25 µL) augmented it by 27.8% relative to the extract alone. Urine (25 µL) exhibited the most significant effect, increasing molybdenum reduction by 30.24%. Likewise, iron reduction was enhanced by 32.00% with plasma and 19.00% with urine. The observed effects were ascribed to interactions between polyphenols and proteins or endogenous antioxidants, such as uric acid, in bodily fluids. The results underscore the significance of physiological context in assessing plant-based antioxidants, indicating that <i>A. unedo</i> extract may exhibit increased <i>bioactivity</i> in vivo due to synergistic interactions with biological components. The study supports the potential of <i>A. unedo</i> as a functional food ingredient and highlights the importance of considering biological fluid interactions during nutraceutical formulation.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":"73 5","pages":"2189-2201"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bab.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580626","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":"Integrating In Vitro Culture, Phytochemical Analysis, and DNA Markers for Comprehensive Characterization of Ocimum sanctum and Ocimum basilicum","authors":"Priya Singh,&nbsp;Hemant Deorukar,&nbsp;Priti Deshmukh,&nbsp;Jyoti Deshpande,&nbsp;Minal Wani","doi":"10.1002/bab.70171","DOIUrl":"10.1002/bab.70171","url":null,"abstract":"<div>\u0000 \u0000 <p>The recognized medicinal potential of <i>Ocimum sanctum</i> (holy basil) and <i>Ocimum basilicum</i> (sweet basil) is largely underpinned by the structural diversity and abundance of their phytochemical constituents. The two species are well documented with regard to their medicinal effects, but there is a lack of comparative investigations linking in vitro biosynthetic potential with genetic diversity. Callus cultures allow for a sustainable alternative that can produce bioactive compounds similar to intact plants without the pressure exerted on natural populations. The present study compared the callus induction response, phytochemical profiles, and RAPD-based molecular diversity of <i>O. sanctum</i> and <i>O. basilicum</i>. Maximum callus proliferation was observed in <i>O. sanctum</i> on MS supplemented with 1.0 mg L⁻¹ 2,4-D + 0.2 mg L⁻¹ BAP, while 0.2 mg L⁻¹ NAA + 0.2 mg L⁻¹ BAP was optimal for <i>O. basilicum</i>. Furthermore, in terms of analysis of the total yield, higher total phenolic and flavonoid contents have been detected in callus extracts and leaves of <i>O. sanctum</i> than in <i>O. basilicum</i>. HPLC analysis confirmed caffeic acid, which is the main compound in both species, rosmarinic acid, and kaempferol, the latter being exclusively found in <i>O. sanctum</i>. RAPD showed various polymorphic banding patterns indicative of polymorphism between the two species. The work correlated the <i>in</i> <i>vitro</i> phytochemical biosynthesis with the molecular level variations in genetics, which can be beneficially grasped for future metabolic exploitation, cultivar selection, and conservation strategies.</p>\u0000 </div>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":"73 5","pages":"2277-2285"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721875","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":"Synthesis of Piperazine-Linked Sulfonamide Derivatives and Their Inhibitory Effects on Glutathione S-Transferase: In Vitro and In Silico Approach","authors":"Tuba Çelik,&nbsp;Adnan Cetin,&nbsp;Fikret Türkan,&nbsp;Ercan Oguz,&nbsp;Elif Akin Kazancioglu,&nbsp;Mustafa Zahrittin Kazancioglu","doi":"10.1002/bab.70172","DOIUrl":"10.1002/bab.70172","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, a series of novel sulfonamide derivatives containing the piperazine moiety was synthesized via the Povarov reaction. Subsequently, these compounds were characterized using ¹H NMR, ¹³C NMR, IR spectroscopy, and mass spectroscopy analysis to determine their structural integrity. The inhibitory effects of these sulfonamide derivatives on the glutathione S-transferase pi 1 (GSTP1-1) enzyme were evaluated, with ethacrynic acid (INN) serving as a standard inhibitor for comparison. The half-maximal inhibitory concentration (IC₅₀) values for secondary amine and synthesized piperazine-linked sulfonamide derivatives (PLSDs) were determined to range from 0.33 to 0.86 µM, indicating significant inhibitory potential. Lineweaver–Burk plots were constructed for each inhibitor, and the inhibition constant (K_i) values were calculated, ranging from 1.443 ± 0.562 to 4.192 ± 0.125 µM. Molecular docking simulations further supported the experimental findings, revealing binding energies between −5.9 and −9.2 kcal/mol, suggesting strong interactions between the sulfonamide derivatives and the GSTP1-1 active site. Molecular dynamics (MDs) studies were performed to further investigate the interaction, orientation, and conformation of the PLSDs over the active site of GSTP1-1. In silico drug-likeness analysis and ADMET predictions of the PLSDs demonstrated that PLSDs showed drug-likeness and had a satisfactory ADMET profile. The structural insights gained from this study offer valuable guidance for the rational design of more potent GSTP1-1 inhibitors, emphasizing the relevance of these scaffolds for future therapeutic developments aimed at targeting GSTP1-1 enzymes.</p>\u0000 </div>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":"73 5","pages":"2286-2298"},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608272","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}