{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:37:40Z","timestamp":1787884660619,"version":"build-2784847793"},"reference-count":65,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"T\u00dcB\u0130TAK 1001 program","doi-asserted-by":"publisher","award":["120Z520"],"award-info":[{"award-number":["120Z520"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004410","name":"T\u00dcB\u0130TAK 1001 program","doi-asserted-by":"publisher","award":["118C270"],"award-info":[{"award-number":["118C270"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004410","name":"T\u00dcB\u0130TAK 1001 program","doi-asserted-by":"publisher","award":["121C063"],"award-info":[{"award-number":["121C063"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Tumor necrosis factor receptor-associated factors (TRAFs) are a protein family with a wide variety of roles and binding partners. Among them, TRAF6, a ubiquitin ligase, possesses unique receptor binding specificity and shows diverse functions in immune system regulation, cellular signaling, central nervous system, and tumor formation. TRAF6 consists of an N-terminal Really Interesting New Gene (RING) domain, multiple zinc fingers, and a C-terminal TRAF domain. TRAF6 is an important therapeutic target for various disorders and structural studies of this protein are crucial for the development of next-generation therapeutics. Here, we presented a TRAF6 N-terminal structure determined at the Turkish light source \u201cTurkish DeLight\u201d to be 3.2 \u00c5 resolution at cryogenic temperature (PDB ID: 8HZ2). This structure offers insight into the domain organization and zinc-binding, which are critical for protein function. Since the RING domain and the zinc fingers are key targets for TRAF6 therapeutics, structural insights are crucial for future research. Separately, we rationally designed numerous new compounds and performed molecular docking studies using this template (PDB ID:8HZ2). According to the results, 10 new compounds formed key interactions with essential residues and zinc ion in the N-terminal region of TRAF6. Molecular dynamic (MD) simulations were performed for 300 ns to evaluate the stability of three docked complexes (compounds 256, 322, and 489). Compounds 256 and 489 was found to possess favorable bindings with TRAF6. These new compounds also showed moderate to good pharmacokinetic profiles, making them potential future drug candidates as TRAF6 inhibitors.<\/jats:p>","DOI":"10.3390\/ph16111608","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T09:46:13Z","timestamp":1699955173000},"page":"1608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Structural Characterization of TRAF6 N-Terminal for Therapeutic Uses and Computational Studies on New Derivatives"],"prefix":"10.3390","volume":"16","author":[{"given":"Omur","family":"Guven","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Ko\u00e7 University, Istanbul 34450, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4847-9711","authenticated-orcid":false,"given":"Belgin","family":"Sever","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4890-3124","authenticated-orcid":false,"given":"Faika","family":"Ba\u015fo\u011flu-\u00dcnal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, European University of Lefke, Northern Cyprus, TR-10, Mersin 99770, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3087-5145","authenticated-orcid":false,"given":"Abdulilah","family":"Ece","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Biruni University, Istanbul 34015, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1225-0720","authenticated-orcid":false,"given":"Hiroshi","family":"Tateishi","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Koga","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9220-2659","authenticated-orcid":false,"given":"Mohamed O.","family":"Radwan","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nefise","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Nanoscience and Nanotechnology, Izmir Katip Celebi University, Izmir 35620, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Can","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and Architecture, Department of Engineering Sciences, Izmir Katip Celebi University, Izmir 35620, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutlu","family":"Dilsiz Aytemir","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, \u0130zmir Katip \u00c7elebi University, Izmir 35620, Turkey"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara 6100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6389-7036","authenticated-orcid":false,"given":"Jun-ichiro","family":"Inoue","sequence":"additional","affiliation":[{"name":"Research Platform Office, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan"},{"name":"Department of Drug Discovery, Science Farm Ltd., Kumamoto 862-0976, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6705-4052","authenticated-orcid":false,"given":"Mikako","family":"Fujita","sequence":"additional","affiliation":[{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9796-7669","authenticated-orcid":false,"given":"Halilibrahim","family":"Ciftci","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Ko\u00e7 University, Istanbul 34450, Turkey"},{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan"},{"name":"Department of Drug Discovery, Science Farm Ltd., Kumamoto 862-0976, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9135-5397","authenticated-orcid":false,"given":"Hasan","family":"DeMirci","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Ko\u00e7 University, Istanbul 34450, Turkey"},{"name":"Koc University Isbank Center for Infectious Diseases (KUISCID), Koc University, Istanbul 34010, Turkey"},{"name":"Stanford PULSE Institute, SLAC National Laboratory, Menlo Park, CA 94025, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0959-440X(00)00167-6","article-title":"Zinc finger proteins: New insights into structural and functional diversity","volume":"11","author":"Laity","year":"2001","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jen, J., and Wang, Y.C. (2016). Zinc finger proteins in cancer progression. J. Biomed. Sci., 23.","DOI":"10.1186\/s12929-016-0269-9"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/protein\/2.3.209","article-title":"A model for the tertiary structure of the 28 residue DNA-binding motif (\u2018zinc finger\u2019) common to many eukaryotic transcriptional regulatory proteins","volume":"2","author":"Gibson","year":"1988","journal-title":"Protein Eng."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"760567","DOI":"10.3389\/fnins.2021.760567","article-title":"Zinc Finger Proteins in Neuro-Related Diseases Progression","volume":"15","author":"Bu","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.bbrc.2021.03.147","article-title":"TRIM37 negatively regulates inflammatory responses induced by virus infection via controlling TRAF6 ubiquitination","volume":"556","author":"Zhao","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1186\/s12935-020-01517-z","article-title":"The relationship between TRAF6 and tumors","volume":"20","author":"Li","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"944528","DOI":"10.3389\/fimmu.2022.944528","article-title":"Novel Findings in Teleost TRAF4, a Protein Acts as an Enhancer in TRIF and TRAF6 Mediated Antiviral and Inflammatory Signaling","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"24871","DOI":"10.1074\/jbc.M802749200","article-title":"The RING domain and first zinc finger of TRAF6 coordinate signaling by interleukin-1, lipopolysaccharide, and RANKL","volume":"283","author":"Lamothe","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/jmcb\/mjs024","article-title":"USP2a negatively regulates IL-1\u03b2- and virus-induced NF-\u03baB activation by deubiquitinating TRAF6","volume":"5","author":"He","year":"2013","journal-title":"J. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s40495-017-0117-y","article-title":"TRAF molecules in inflammation and inflammatory diseases","volume":"4","author":"Lalani","year":"2018","journal-title":"Curr. Pharmacol. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6482","DOI":"10.1038\/sj.onc.1204788","article-title":"Tumor necrosis factor receptor-associated factors (TRAFs)","volume":"20","author":"Bradley","year":"2001","journal-title":"Oncogene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.dci.2010.08.013","article-title":"Litopenaeus vannamei tumor necrosis factor receptor-associated factor 6 (TRAF6) responds to Vibrio alginolyticus and white spot syndrome virus (WSSV) infection and activates antimicrobial peptide genes","volume":"35","author":"Wang","year":"2011","journal-title":"Dev. Comp. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/imr.12302","article-title":"Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system","volume":"266","author":"Walsh","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1006\/excr.1999.4733","article-title":"Tumor necrosis factor receptor-associated factor (TRAF) family: Adapter proteins that mediate cytokine signaling","volume":"254","author":"Inoue","year":"2000","journal-title":"Exp. Cell Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"145","DOI":"10.2183\/pjab.97.009","article-title":"TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-\u03baB activation","volume":"97","author":"Yamamoto","year":"2021","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1101\/gad.1228704","article-title":"Signaling to NF-kappaB","volume":"18","author":"Hayden","year":"2004","journal-title":"Genes Dev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Park, M.H., and Hong, J.T. (2016). Roles of NF-\u03baB in Cancer and Inflammatory Diseases and Their Therapeutic Approaches. Cells, 5.","DOI":"10.3390\/cells5020015"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"144132","DOI":"10.1016\/j.gene.2019.144132","article-title":"Role of the NF-\u03baB signaling pathway in the pathogenesis of colorectal cancer","volume":"726","author":"Soleimani","year":"2020","journal-title":"Gene"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1038\/s41467-017-01665-3","article-title":"The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1","volume":"8","author":"Middleton","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13046-017-0502-8","article-title":"Cinchonine induces apoptosis of HeLa and A549 cells through targeting TRAF6","volume":"36","author":"Qi","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Khusbu, F.Y., Zhou, X., Roy, M., Chen, F.Z., Cao, Q., and Chen, H.C. (2020). Resveratrol induces depletion of TRAF6 and suppresses prostate cancer cell proliferation and migration. Int. J. Biochem. Cell Biol., 118.","DOI":"10.1016\/j.biocel.2019.105644"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.ijbiomac.2021.04.081","article-title":"Identification of a new TRAF6 inhibitor for the treatment of hepatocellular carcinoma","volume":"182","author":"Li","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1111\/cas.15302","article-title":"TRAF6 regulates the signaling pathway influencing colorectal cancer function through ubiquitination mechanisms","volume":"113","author":"Guangwei","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3892\/etm.2021.11104","article-title":"Benzoyl-xanthone derivative induces apoptosis in MCF-7 cells by binding TRAF6","volume":"23","author":"Zhao","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30861","DOI":"10.1074\/jbc.M802525200","article-title":"Tumor necrosis factor receptor-associated factor 6 is an intranuclear transcriptional coactivator in osteoclasts","volume":"283","author":"Bai","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, T., Li, Y., Li, J.W., Qin, Y.H., Zhai, H., Feng, B., Li, H., Zhang, N.N., and Yang, C.S. (2022). Expression of TRAF6 in peripheral blood B cells of patients with myasthenia gravis. BMC Neurol., 22.","DOI":"10.1186\/s12883-022-02833-9"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3808","DOI":"10.1074\/jbc.RA119.011215","article-title":"TNF receptor-associated factor 6 interacts with ALS-linked misfolded superoxide dismutase 1 and promotes aggregation","volume":"295","author":"Semmler","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"629910","DOI":"10.3389\/fnmol.2021.629910","article-title":"Pathogenic Functions of Tumor Necrosis Factor Receptor-Associated Factor 6 Signaling Following Traumatic Brain Injury","volume":"14","author":"Huang","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s10571-021-01045-y","article-title":"TRAF6 Contributes to CFA-Induced Spinal Microglial Activation and Chronic Inflammatory Pain in Mice","volume":"42","author":"Lu","year":"2022","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s12035-021-02666-6","article-title":"The E3 Ubiquitin Ligase TRAF6 Interacts with the Cellular Prion Protein and Modulates Its Solubility and Recruitment to Cytoplasmic p62\/SQSTM1-Positive Aggresome-Like Structures","volume":"59","author":"Masperone","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1002\/cmdc.201700399","article-title":"A Dithiol Compound Binds to the Zinc Finger Protein TRAF6 and Suppresses Its Ubiquitination","volume":"12","author":"Koga","year":"2017","journal-title":"ChemMedChem"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1016\/j.bmcl.2019.06.050","article-title":"Minimum structural requirements for inhibitors of the zinc finger protein TRAF6","volume":"29","author":"Radwan","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Guven, O., Ciftci, H., and DeMirci, H. (2023, November 08). Tumor Necrosis Factor Receptor Associated Factor 6 (TRAF6) N-terminal Domain. PDB Entry\u20148HZ2. Available online: https:\/\/doi.org\/10.2210\/pdb8HZ2\/pdb.","DOI":"10.2210\/pdb8hz2\/pdb"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8123","DOI":"10.1038\/s41598-023-33989-0","article-title":"Rapid and efficient ambient temperature X-ray crystal structure determination at Turkish Light Source","volume":"13","author":"Gul","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/nsmb.1605","article-title":"E2 interaction and dimerization in the crystal structure of TRAF6","volume":"16","author":"Yin","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1021\/jm00017a011","article-title":"Novel zinc chelators with dual activity in the inhibition of the kappa B site-binding proteins HIV-EP1 and NF-kappa","volume":"38","author":"Otsuka","year":"1995","journal-title":"Br. J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0968-0896(96)00203-9","article-title":"Synthetic inhibitors of regulatory proteins involved in the signaling pathway of the replication of human immunodeficiency virus 1","volume":"5","author":"Otsuka","year":"1997","journal-title":"Bioorg. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1021\/jm950831t","article-title":"Metal-chelating inhibitors of a zinc finger protein HIV-EP1. Remarkable potentiation of inhibitory activity by introduction of SH groups","volume":"39","author":"Fujita","year":"1996","journal-title":"J. Med. Chem."},{"key":"ref_39","first-page":"613","article-title":"An anti-HIV-1 compound that increases steady-state expression of apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G","volume":"28","author":"Ejima","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1016\/j.bmcl.2017.06.047","article-title":"A novel inhibitor of farnesyltransferase with a zinc site recognition moiety and a farnesyl group","volume":"27","author":"Tanaka","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1248\/cpb.c21-00701","article-title":"A new inhibitor of ADAM17 composed of a zinc-binding dithiol moiety and a specificity pocket-binding appendage","volume":"69","author":"Tateishi","year":"2021","journal-title":"Chem. Pharm. Bull."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ece, A. (2023). Computer-aided drug design. BMC Chem., 17.","DOI":"10.1186\/s13065-023-00939-w"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"G\u00fcle\u00e7, \u00d6., T\u00fcrke\u015f, C., Arslan, M., Demir, Y., Dincer, B., Ece, A., and Beydemir, \u015e. (2023). Novel beta-lactam substituted benzenesulfonamides: In vitro enzyme inhibition, cytotoxic activity and in silico interactions. J. Biomol. Struct. Dyn., 1\u201319.","DOI":"10.1080\/07391102.2023.2240889"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"\u00c7elik Onar, H., \u00d6zden, E.M., Taslak, H.D., G\u00fcl\u00e7in, \u0130., Ece, A., and Er\u00e7a\u011f, E. (2023). Novel coumarin-chalcone derivatives: Synthesis, characterization, antioxidant, cyclic voltammetry, molecular modelling and biological evaluation studies as acetylcholinesterase, \u03b1-glycosidase, and carbonic anhydrase inhibitors. Chem. Biol. Interact., 383.","DOI":"10.1016\/j.cbi.2023.110655"},{"key":"ref_45","unstructured":"(Schr\u00f6dinger Release 2016-2: QikProp, 2016). Schr\u00f6dinger Release 2016-2: QikProp."},{"key":"ref_46","unstructured":"(2023, August 30). SwissADME. Available online: http:\/\/www.swissadme.ch."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.2174\/1570159X16666180412094655","article-title":"Roles of TRAF6 in Central Nervous System","volume":"16","author":"Dou","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1080\/15548627.2018.1474995","article-title":"Inhibition of TRAF6 ubiquitin-ligase activity by PRDX1 leads to inhibition of NFKB activation and autophagy activation","volume":"14","author":"Min","year":"2018","journal-title":"Autophagy"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1517\/14728220903431069","article-title":"The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy","volume":"14","author":"Lin","year":"2010","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17071","DOI":"10.1038\/cddiscovery.2017.71","article-title":"Zinc-finger proteins in health and disease","volume":"3","author":"Cassandri","year":"2017","journal-title":"Cell Death Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1093\/nar\/gkg161","article-title":"Structural classification of zinc fingers: Survey and summary","volume":"31","author":"Krishna","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/s41392-022-01152-2","article-title":"The RING finger protein family in health and disease","volume":"7","author":"Cai","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"101158","DOI":"10.1016\/j.xpro.2022.101158","article-title":"Protocol for structure determination of SARS-CoV-2 main protease at near-physiological-temperature by serial femtosecond crystallography","volume":"3","author":"Ertem","year":"2022","journal-title":"STAR Protoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1107\/S0907444905034207","article-title":"Cryocooling and radiation damage in macromolecular crystallography","volume":"62","author":"Garman","year":"2006","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.55730\/1300-0152.2637","article-title":"Cryogenic X-ray crystallographic studies of biomacromolecules at Turkish Light Source \u201cTurkish DeLight\u201d","volume":"47","author":"Atalay","year":"2022","journal-title":"Turk. J. Biol."},{"key":"ref_57","unstructured":"Rigaku (2023, November 08). CrysAlisPro Software System, Version 1.171.42.35a. Available online: https:\/\/www.rigaku.com."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1107\/S0021889807021206","article-title":"Phaser crystallographic software","volume":"40","author":"McCoy","year":"2007","journal-title":"J. Appl. Crystallogr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: A comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: Model-building tools for molecular graphics","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_61","unstructured":"(The PyMOL Molecular Graphics System, Version 2.5.2, 2023). The PyMOL Molecular Graphics System, Version 2.5.2."},{"key":"ref_62","unstructured":"(Schr\u00f6dinger Release 2016-2, 2016). Schr\u00f6dinger Release 2016-2."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ciftci, H., Sever, B., Ayan, E., Can, M., DeMirci, H., Otsuka, M., TuYuN, A.F., Tateishi, H., and Fujita, M. (2022). Identification of New L-Heptanoylphosphatidyl Inositol Pentakisphosphate Derivatives Targeting the Interaction with HIV-1 Gag by Molecular Modelling Studies. Pharmaceuticals, 15.","DOI":"10.3390\/ph15101255"},{"key":"ref_64","unstructured":"(Schr\u00f6dinger Release 2023-3, 2023). Schr\u00f6dinger Release 2023-3."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"234505","DOI":"10.1063\/1.2121687","article-title":"A general purpose model for the condensed phases of water: TIP4P\/2005","volume":"123","author":"Abascal","year":"2005","journal-title":"J. Chem. Phys."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/11\/1608\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:23:00Z","timestamp":1760131380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/11\/1608"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,14]]},"references-count":65,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ph16111608"],"URL":"https:\/\/doi.org\/10.3390\/ph16111608","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,14]]}}}