{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:20:17Z","timestamp":1779200417977,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["R.12014\/06\/2022\u2010HR"],"award-info":[{"award-number":["R.12014\/06\/2022\u2010HR"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The emergence of multidrug\u2010resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    necessitates novel antimicrobial strategies. This study reports the synthesis and evaluation of thiazolyl benzenesulfonamide\u2010derived synthetic kinase inhibitors targeting thymidine kinase (TK), essential for bacterial DNA metabolism. Derivatives were synthesized via aromatic ring modifications and characterized by\n                    <jats:sup>1<\/jats:sup>\n                    H\/\n                    <jats:sup>13<\/jats:sup>\n                    C NMR. Compound DSA3 exhibited significant interaction with TK. Fluorescence binding assays confirmed high\u2010affinity DSA3\u2013TK binding, corroborated by isothermal titration calorimetry revealing exothermic, spontaneous complex formation (favorable \u0394\n                    <jats:italic>G<\/jats:italic>\n                    , \u0394\n                    <jats:italic>H<\/jats:italic>\n                    , \u0394\n                    <jats:italic>S<\/jats:italic>\n                    ). Molecular docking positioned DSA3 within the TK ATP\u2010binding pocket, forming hydrogen bonds and hydrophobic contacts with key residues, including the catalytic residue Glu89. Molecular dynamics simulations indicated DSA3 stabilizes TK structure by inducing minimal conformational perturbation. Crucially, DSA3 potently inhibited the ATPase activity of TK with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 6.99\u00a0\u00b5M, disrupting its enzymatic function. In vitro antimicrobial testing showed the MIC value of 50\u00a0\u00b5M, demonstrating the potent activity of DSA3 against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    (ATCC 29213). These integrated findings validate DSA3 as a promising TK inhibitor, effectively impeding bacterial growth by targeting DNA synthesis. This highlights the potential of DSA3 as a novel therapeutic agent against multidrug\u2010resistant\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infections, offering a mechanism to circumvent prevailing resistance.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202501600","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T18:15:21Z","timestamp":1753208121000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Thiazolyl Benzenesulfonamide Derivative as a Novel Inhibitor of Thymidine Kinase: Promising Therapeutics Against\n                    <i>Staphylococcus aureus<\/i>"],"prefix":"10.1002","volume":"22","author":[{"given":"Rajesh K.","family":"Hadiya","sequence":"first","affiliation":[{"name":"Department of Biological Sciences &amp; Engineering Indian Institute of Technology Gandhinagar, Palaj  Gandhinagar Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anam","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Centre For Interdisciplinary Research in Basic Sciences Jamia Millia Islamia  Jamia Nagar New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics School of Science, Xi'an Jiaotong\u2010Liverpool University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faez Iqbal","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics School of Science, Xi'an Jiaotong\u2010Liverpool University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Ali","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Jamia Hamdard  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Renuka","sequence":"additional","affiliation":[{"name":"Sushen Medicamentos Pvt. Ltd.  Ahmedabad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahbaz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics School of Science, Xi'an Jiaotong\u2010Liverpool University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saba","family":"Noor","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics School of Science, Xi'an Jiaotong\u2010Liverpool University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaushik","family":"Shah","sequence":"additional","affiliation":[{"name":"Sushen Medicamentos Pvt. Ltd.  Ahmedabad Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-2023","authenticated-orcid":false,"given":"Bhaskar","family":"Datta","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences &amp; Engineering Indian Institute of Technology Gandhinagar, Palaj  Gandhinagar Gujarat India"},{"name":"Department of Chemistry Indian Institute of Technology Gandhinagar, Palaj  Gandhinagar Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3663-4940","authenticated-orcid":false,"given":"Md. Imtaiyaz","family":"Hassan","sequence":"additional","affiliation":[{"name":"Centre For Interdisciplinary Research in Basic Sciences Jamia Millia Islamia  Jamia Nagar New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/bjbs.2023.11387"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4572"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176667"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(82)90207-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00941"},{"key":"e_1_2_9_7_1","first-page":"298","article-title":"Giardia Intestinalis Thymidine Kinase Is a High\u2010Affinity Enzyme Crucial for DNA Synthesis and an Exploitable Target for Drug Discovery","author":"Krakovka S.","year":"2022","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.29356\/jmcs.v65i2.1464"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006297"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05115-14"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02832.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257770701845238"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.10.021"},{"key":"e_1_2_9_14_1","first-page":"2171","article-title":"Antibacterial Activity of Thiazole and Its Derivatives","volume":"12","author":"Mohanty P.","year":"2022","journal-title":"Biointerface Res Appl Chem"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00277a002"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.11.017"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph13060118"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1RA03882F"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05617.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-022-03446-4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00952"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf070905x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-5394(01)00170-0"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1214330110"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.2c00100"},{"key":"e_1_2_9_26_1","first-page":"397","article-title":"Therapeutic Uses of Metronidazole and Its Side Effects: An Update","volume":"23","author":"Ceruelos A. 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