Zeitschrift fur Naturforschung. C, Journal of biosciences最新文献

{"title":"Design, synthesis, and biological evaluation of pyrimidine linked fused thiazole-isoxazole conjugates as dual cholinesterase inhibitors for Alzheimer's disease.","authors":"Yousaf Khan, Mujeeb Ul Naeem, Syeda Farwa Naqvi, Briha Fatima, Rafaqat Hussain, Hassam Uddin, Tariq Aziz, Ammena Y Binsaleh, Nawal Al-Hoshani, Hayam A Alwabsi","doi":"10.1515/znc-2026-0143","DOIUrl":"https://doi.org/10.1515/znc-2026-0143","url":null,"abstract":"<p><p>Alzheimer's disease (AD) affects over 55 million individuals worldwide, yet approved pharmacotherapies remain limited to symptomatic relief. Dual inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) offers a validated approach to restoring cholinergic tone. However, structurally differentiated inhibitors with favorable selectivity profiles are critically needed. Here, we report a series of pyrimidine clubbed thiazolo[4,5-c]isoxazole framework that functions as potent dual cholinesterase inhibitors with low-micromolar activity against both AChE and BuChE. Lead compound-<b>1</b> demonstrated IC₅₀ values of 6.19 ± 0.60 μM (AChE) and 8.64 ± 0.91 μM (BuChE) showing promising performance over the reference donepezil (AChE IC₅₀ = 19.38 ± 0.98 μM, BuChE IC₅₀ = 27.54 ± 1.34 μM). Furthermore, structure-activity relationship analysis identified electron-withdrawing (<i>p</i>-CF₃, <i>p</i>-F, <i>o,p</i>-Cl, <i>p</i>-NO₂) and electron-donating (-OH) aryl substituents as principal modulators of inhibitory potency. Moreover, molecular docking against human AChE and BuChE crystal structures revealed dual engagement of the catalytic anionic site and peripheral anionic site through hydrogen-bonding and π-π stacking interactions. In silico ADMET profiling confirmed electronic reactivity and drug-likeness of lead compounds. These findings establish pyrimidine-clubbed thiazolo[4,5-c]isoxazole as a mechanistically grounded scaffold with translational potential for next-generation anti-Alzheimer therapeutics.</p>","PeriodicalId":520830,"journal":{"name":"Zeitschrift fur Naturforschung. C, Journal of biosciences","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating <i>in vitro</i> and <i>in silico</i> correlation of thiazole-based carboxamide derivatives as promising SARS-CoV-2 papain-like protease inhibitors: a versatile approach for COVID-19 therapy.","authors":"Imran Khan, Rafaqat Hussain, Hina Sarfraz, Umair Khurshid, Yousuf Rehman Buzdar, Sumaira Naz, Ammena Y Binsaleh, Nawal Al-Hoshani, Huda A Alqahtani, Rasha Alonaizan, Ilham M Alshiraihi","doi":"10.1515/znc-2026-0126","DOIUrl":"https://doi.org/10.1515/znc-2026-0126","url":null,"abstract":"<p><p>A new series of thiazole-based carboxamide derivatives (<b>5-12</b>) was designed, synthesized with structural elucidation performed using standard spectroscopic techniques including NMR and HRMS. The synthesized compounds were evaluated for their inhibitory activity against SARS-CoV-2 papain-like protease (PL^pro) and compared with the reference inhibitor <b>GRL0617</b> (IC₅₀ = 2.73 ± 2.20 µM). Among the tested compounds, compounds <b>(8)</b> (IC₅₀ = 1.94 ± 1.50 µM) and <b>(6)</b> (IC₅₀ = 2.53 ± 1.90 µM) exhibited the most potent inhibitory activity, outperforming or matching the reference inhibitor, while the remaining compounds showed moderate to good PLpro inhibition. Structure-activity relationship analysis was supported by molecular docking studies, which demonstrated that compound 8 possessed the strongest binding affinity (-7.875 kcal/mol), forming key hydrogen bonds with Gly163 and Gly271. Compound <b>(6)</b> also showed favorable binding (-7.426 kcal/mol), establishing similar hydrogen bonding interactions together with additional hydrophobic contacts within the active site. Density functional theory (DFT) calculations provided insights into the electronic properties underlying molecular reactivity and stability, whereas <i>in silico</i> ADME analysis predicted favorable pharmacokinetic characteristics and drug-likeness. Collectively, these experimental and computational findings identify thiazole-based carboxamide derivatives, particularly compounds <b>(8)</b> and <b>(6)</b>, as promising candidates for the development of potent SARS-CoV-2 PL^pro inhibitors.</p>","PeriodicalId":520830,"journal":{"name":"Zeitschrift fur Naturforschung. C, Journal of biosciences","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the phytochemical composition of <i>Curcuma longa</i>, <i>Azadirachta indica</i>, and <i>Asparagus racemosus</i> using network pharmacology and molecular docking approaches for ovarian cancer therapy.","authors":"Seneha Santoshi, Aastha Tanwar, Riddhi Bahri, Navya Aggrawal, Deepak Ganjewala, Hina Bansal","doi":"10.1515/znc-2026-0118","DOIUrl":"https://doi.org/10.1515/znc-2026-0118","url":null,"abstract":"<p><p>Given that ovarian cancer is a major health concern for women worldwide, we explored the potential of Indian medicinal plants, namely <i>Curcuma longa</i> (Turmeric), <i>Azadirachta indica</i> (Neem), and <i>Asparagus racemosus</i> (Shatavari) <i>via</i> a combined approach of network pharmacology and molecular docking. Initially, bioactive phytochemicals of these plants were sourced from the IMPPAT and SwissTargetPrediction databases, resulting in the identification of 202 compounds along with 1,124 corresponding protein targets. These were then compared with ovarian cancer-related genes obtained from the GeneCards database, leading to the identification of 885 common targets. A protein-protein interaction network was constructed and analyzed using Cytoscape to identify the cluster modules. Additionally, gene ontology and pathway enrichment analyses revealed the multifaceted nature of ovarian cancer, indicating its disruptive impact on various cellular processes, signaling pathways, immune responses, and metabolic regulations. Importantly, EGFR, PIK3CA, JAK2, and PIK3CD were identified as crucial therapeutic nodes within the network. Subsequent molecular docking recognized the strong binding affinity between the active compounds and these key targets, thereby supporting the network analysis. In conclusion, the study highlighted the therapeutic action of <i>C. longa</i>, <i>A. indica</i>, and <i>A. racemosus</i> in combating ovarian cancer and promoting the development of plant-based treatments for this cancer.</p>","PeriodicalId":520830,"journal":{"name":"Zeitschrift fur Naturforschung. C, Journal of biosciences","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148870098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multitargeted drug strategies for Alzheimer's and Parkinson's diseases.","authors":"Azmat Ullah Khan, Abdullah Abdullah, Syeda Farwa Naqvi, Hadia Tahir, Hira Khalid, Hina Sarfraz, Yousaf Khan","doi":"10.1515/znc-2026-0116","DOIUrl":"https://doi.org/10.1515/znc-2026-0116","url":null,"abstract":"<p><p>Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are multifactorial diseases that are characterized by several interconnected pathological mechanisms, such as the aggregation of amyloid-beta (Aβ), hyperphosphorylation of tau, accumulation of α-synuclein, oxidative stress, mitochondrial dysfunction, neuroinflammation, and neurotransmitter imbalance. Conventional single-target therapies failed to produce significant clinical effects due to the fact that they target only individual disease pathways. Thus, the multitarget-directed ligand (MTDL) strategy has become an attractive therapeutic option, and MTDLs can act on several pathological targets simultaneously. Recent advances in multitarget drug development for AD and PD targeting compounds targeting Aβ, BACE1, MAO-B, cholinesterases, metal-ion dyshomeostasis, oxidative stress, and inflammatory pathways are reviewed. A few potential candidates, such as GV-971, Prasinezumab, Huperzine A, curcumin derivatives, and hybrids of MAO-B inhibitors, have shown neuroprotective and cognitive effects in preclinical and clinical studies. There are significant advances in the clinical pipeline, with over 180 clinical trials for AD and over 130 clinical trials for PD testing multitarget or disease-modifying strategies. The review also highlights the growing importance of computer-aided drug design (CADD), artificial intelligence (AI), and machine learning (ML) in speeding up the discovery of MTDL, optimizing their pharmacokinetic profiles, and predicting multitarget interactions. However, there are still major obstacles to be overcome, such as the ability to cross the blood-brain barrier, optimizing the pharmacokinetics, the difficulties of transferring from the animal to the human model, and the complexity of the regulatory process. New strategies based on nanomedicine, biomarker-driven trials, personalized medicine, and drug repurposing will enhance therapeutic precision and clinical success.</p>","PeriodicalId":520830,"journal":{"name":"Zeitschrift fur Naturforschung. C, Journal of biosciences","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148852340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical profiling, antimicrobial, cytotoxic and apoptotic effects of <i>Glycyrrhiza glabra</i> ethanolic extract.","authors":"Rumeysa Olgun, Ceren Başkan, Faruk Karahan, Ömer Ertürk, Birsen Aydın, Belgin Sırıken, Dudu Duygu Kılıç","doi":"10.1515/znc-2025-0246","DOIUrl":"https://doi.org/10.1515/znc-2025-0246","url":null,"abstract":"<p><p><i>Glycyrrhiza glabra</i> L. is a medicinal plant rich in bioactive compounds, yet detailed studies on its antimicrobial, cytotoxic, and apoptotic properties remain limited. This research evaluated these effects using an ethanolic extract of <i>G. glabra</i>. The extract was prepared via Soxhlet extraction, and its chemical constituents were identified using gas chromatography-mass spectrometry (GC-MS). <i>In vitro</i> antimicrobial activity was tested against various microorganisms through well diffusion and microdilution methods, while minimum bactericidal and fungicidal concentrations were determined using agar plate assays. Cytotoxicity on HepG2 human hepatocellular carcinoma cells was assessed with the MTT assay. Additionally, the expression of apoptosis-related genes (<i>p53</i>, <i>Bax</i>, and <i>Bcl-2</i>) was analyzed by quantitative real-time PCR. GC-MS results revealed a total of 28 compounds, with 2,8-dimethyl-7,8-dihydro-6H-cyclohepta (18.59 %) and thiophene (16.58 %) as the major constituents. The extract showed strong antimicrobial effects, especially against Gram-positive bacteria such as <i>Listeria monocytogenes</i>, <i>Enterococcus faecalis</i>, and <i>Streptococcus mutans</i>. Among Gram-negative strains, <i>Salmonella enteritidis</i> was the most susceptible. Cytotoxic activity against HepG2 cells was observed, with an IC₅₀ value of 206.8 µg/mL. This effect was associated with increased expression of <i>p53</i> and <i>Bax</i> and decreased <i>Bcl-2</i> levels, indicating apoptosis. The ethanolic extract of <i>G. glabra</i> shows strong antimicrobial and cytotoxic potential and may be explored as a potential chemopreventive agent.</p>","PeriodicalId":520830,"journal":{"name":"Zeitschrift fur Naturforschung. C, Journal of biosciences","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational design and biological evaluation of naturally inspired indole-oxadiazole derivatives as potent COX inhibitors.","authors":"Burak Kuzu, Derya Osmaniye, Büşra Korkut-Çelikateş, Zafer Asım Kaplancıklı","doi":"10.1515/znc-2026-0075","DOIUrl":"https://doi.org/10.1515/znc-2026-0075","url":null,"abstract":"<p><p>Indole-oxazole and indole-oxadiazole scaffolds, inspired by natural products, provide versatile platforms for the development of selective COX inhibitors. In this study, a novel series of indol-oxadiazole derivatives was rationally designed by incorporating N-alkyl-substituted indole moieties at the 5-position and optimizing aryl substitutions at the 2-position of the oxadiazole core. The synthesized compounds were systematically evaluated for COX-1 and COX-2 inhibition <i>in vitro</i>, revealing potent and selective activity. The compounds exhibited potent <i>in vitro</i> COX inhibition, with <b>IO-2</b> showing balanced dual activity against COX-1 (IC₅₀ = 0.198 ± 0.022 µM) and COX-2 (IC₅₀ = 0.158 ± 0.028 µM), and <b>IO-13</b> displaying strong COX-1 inhibition (IC₅₀ = 0.175 ± 0.063 µM). Celecoxib served as the reference COX-2 inhibitor (IC₅₀ = 0.119 ± 0.055 µM). Molecular docking and dynamics simulations provided insights into binding interactions and the stability of the COX complex within the COX active site. Selected derivatives were well tolerated in healthy cell lines, indicating favorable safety profiles. Structure-activity relationship analysis highlighted the critical role of the indole nucleus and strategic oxadiazole substitutions in modulating COX inhibitory potency and selectivity. These findings establish indole-oxadiazoles as a promising scaffold for selective COX inhibition and a foundation for future rational drug design.</p>","PeriodicalId":520830,"journal":{"name":"Zeitschrift fur Naturforschung. C, Journal of biosciences","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxicity and antimicrobial activity of platinum(II) complexes based on the ligand precursor 2-phenyl-6-(1,2,3-triazol-4-yl)pyridine - influence of substituent and ancillary ligand on selectivity and activity.","authors":"Marian Hebenbrock, Soňa Gurská, Kateřina Bogdanová, Kristýna Rešová, Milan Kolář, Felix Boisten, Marián Hajdúch, Petr Džubák, Jens Müller","doi":"10.1515/znc-2025-0262","DOIUrl":"https://doi.org/10.1515/znc-2025-0262","url":null,"abstract":"<p><p>The development of metal-based anticancer agents has been a significant area of research since the discovery of cisplatin's cytostatic effects. In this study, we investigate the cytotoxicity of tridentate ligands derived from 2-phenyl-6-(1,2,3-triazol-4-yl)pyridine and their platinum(II) and palladium(II) complexes against various human cancer cell lines and normal fibroblasts. Several complexes exhibit high cytotoxicity, particularly against acute T-lymphoblastic leukemia cells (CCRF-CEM). Notably, a platinum(II) complex containing an acylpyrrolidine ligand demonstrates remarkable cancer cell selectivity with a sub-micromolar IC₅₀ value of 0.17 μM. Cell cycle analysis revealed that these compounds induce apoptosis and affect DNA/RNA synthesis. Additionally, some complexes show significant antimicrobial activity against Gram-positive bacteria and yeast. Our findings highlight the potential of these metal complexes as selective anticancer agents and underscore the importance of further mechanistic studies.</p>","PeriodicalId":520830,"journal":{"name":"Zeitschrift fur Naturforschung. C, Journal of biosciences","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148059527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure activity relationship-guided scaffold hopping for identification of novel thiadiazole derivatives as potent SARS-CoV-2 Mpro inhibitors.","authors":"Maher S Alwethaynani, Khaled Alzhrani, Hina Sarfraz, Tahir Ali Chohan, Asma Sardar, Maha Abdullah Alwaili, Nawal Al-Hoshani, Hayam A Alwabsi, Sumaira Naz, Rafaqat Hussain","doi":"10.1515/znc-2026-0045","DOIUrl":"https://doi.org/10.1515/znc-2026-0045","url":null,"abstract":"<p><p>The ongoing COVID-19 pandemic has presented enormous challenges to worldwide healthcare systems, and effective therapeutic strategies must accompany mass vaccination efforts. In this context, Mpro (the main protease of SARS-CoV-2) is arguably one of the most promising molecular targets for antiviral drug development because it is responsible for processing viral polyproteins and replicating the virus. In this study, a rational design approach was employed to develop a novel series of thiadiazole-based derivatives as potential Mpro inhibitors. A total of compounds (<b>5a-f</b>, <b>9a-d</b>, and <b>12a-j</b>) were synthesized through three systematically organized synthetic schemes. Each stage of the design strategy incorporated progressive structural modifications to establish a clear structure activity relationship (SAR) and enhance inhibitory potency. The synthesized compounds were evaluated for their <i>in vitro</i> inhibitory activity against SARS-CoV-2 Mpro. Some derivatives like <b>5b</b> (IC₅₀ = 44.63 ± 1.20 µM), <b>12c</b> (IC₅₀ = 39.25 ± 1.60 μM), <b>12a</b> (IC₅₀ = 41.93 ± 1.90 μM), showed good inhibitory activity as compared to reference drug Nirmatrelvir (IC₅₀ = 58.4 ± 8.6 μM). Molecular docking analysis supported the experimental data by confirming stable binding of the synthesized compounds within the Mpro active site through key hydrogen-bonding and hydrophobic interactions.</p>","PeriodicalId":520830,"journal":{"name":"Zeitschrift fur Naturforschung. C, Journal of biosciences","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calofrasolide A, a new pyranocoumarin from the stem bark of <i>Calophyllum fraseri</i> M.R.Hend. & Wyatt-Sm. and their antimicrobial and antibiofilm activities.","authors":"Nur Nabilah Mohd Zaini, Wan Mohd Nuzul Hakimi Wan Salleh, Nurunajah Ab Ghani, Abubakar Siddiq Salihu, Mohd Hafiz Arzmi, Nurulfazlina Edayah Rasol, Sherali Kuziev, Feruzbek Khasanov","doi":"10.1515/znc-2025-0314","DOIUrl":"https://doi.org/10.1515/znc-2025-0314","url":null,"abstract":"<p><p>A new pyranocoumarin, Calofrasolide A (<b>1</b>), was isolated from the stem bark of <i>Calophyllum fraseri</i>, together with the known constituents β-sitosterol, stigmasterol, friedelin, and lupeol. The structure of the new compound was established through comprehensive spectroscopic analyses and confirmed by comparison with reported data. Compound <b>1</b> was evaluated for antimicrobial and antibiofilm activities using microdilution and crystal-violet assays. It exhibited notable antimicrobial activity, with MIC values of 62.5 μg/mL against <i>Candida albicans</i> and <i>Streptococcus mutans</i>. In the antibiofilm assays, compound <b>1</b> demonstrated pronounced inhibitory effects, suppressing <i>C. albicans</i> biofilm formation by 30.25 ± 1.04 % and <i>S. mutans</i> biofilms by 78.37 ± 0.22 %. Molecular docking studies supported the experimental findings, revealing favourable binding (LBE = -8.5 kcal/mol) within the active sites of ERG11 (5TZ1) and GtfB (8FK4). These findings highlight Calofrasolide A as a promising pyranocoumarin scaffold with potential antimicrobial and antibiofilm relevance, particularly against oral pathogenic infections.</p>","PeriodicalId":520830,"journal":{"name":"Zeitschrift fur Naturforschung. C, Journal of biosciences","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the biodegradation potential of Nudix hydrolase from <i>Bacillus paranthracis</i> via different approaches.","authors":"Muhammad Naveed, Nimra Hanif, Minahil Zahid, Muhammad Asjad Haseeb, Maida Salah Ud Din, Muhammad Nouman Majeed, Ayaz Ali Khan, Manal F Elkhadragy, Ashwag Shami, Hayam A Alwabsi","doi":"10.1515/znc-2025-0301","DOIUrl":"10.1515/znc-2025-0301","url":null,"abstract":"<p><p>The Nudix hydrolase from <i>Bacillus paranthracis</i> MBBL1 was investigated using in silico approaches. Polyfluoroalkyl substances (PFAS) are persistent environmental contaminants associated with serious health and ecological risks because of their stable chemical nature and strong resistance to breakdown. The enzyme sequence was retrieved from NCBI (Accession No. MFQ6175622.1), and its secondary structure revealed 33 alpha-helices, 50 beta-strands, and 66 coil regions, suggesting a balanced structural conformation. Tertiary structure prediction using AlphaFold3 achieved a high-confidence model with 94.5 % residues in the most favored regions of the Ramachandran plot and an ERRAT quality score of 96.99 %, validating its stereochemical reliability. Physicochemical profiling indicated a molecular weight of 17 kDa, a theoretical pI of 4.86, and a GRAVY index of -0.245, confirming its hydrophilic and slightly acidic nature. Two active-sites were predicted by PrankWeb, with Pocket 1 showing a high binding score of 6.46. Molecular docking against twelve PFAS derivatives showed favorable binding affinities ranging from -6.4 to -9.5 kcal/mol. Perfluorodecanoic acid demonstrated the strongest interaction (-9.5 kcal/mol), followed by H-PFOS (-9.0 kcal/mol) and perfluorooctanesulfonic acid (-8.8 kcal/mol). Interaction analysis identified key residues such as ALA22, THR40, ASP42, and ASN133 forming multiple hydrogen, halogen, and electrostatic bonds. These findings suggest that Nudix hydrolase may have structural and functional attributes relevant to PFAS biodegradation. Acknowledging the computational nature of this study, experimental validation will be required to confirm biodegradation activity.</p>","PeriodicalId":520830,"journal":{"name":"Zeitschrift fur Naturforschung. C, Journal of biosciences","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}