{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:39:16Z","timestamp":1789155556366,"version":"build-2803163510"},"reference-count":26,"publisher":"Walter de Gruyter GmbH","issue":"7-8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Thymidine phosphorylase (TP) is a key enzyme involved in pyrimidine nucleoside metabolism and plays a significant role in angiogenesis, tumor progression, and metastasis. In this study, we synthesized 12 pyrazole-based thiadiazole and thiazole derivatives and evaluated their\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    TP inhibitory activity. The compounds exhibited IC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 36.67\u00a0\u00b1\u00a03.50\u202f\u03bcM to 61.23\u00a0\u00b1\u00a03.20\u202f\u03bcM, with several derivatives showing comparable or superior activity to the standard inhibitor 7-deazaxanthine (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a038.68\u00a0\u00b1\u00a01.12\u202f\u03bcM). Structure\u2013activity relationship (SAR) analysis revealed that electron-withdrawing halogen substituents on the aromatic ring enhanced TP inhibition, likely due to increased binding affinity at the TP active site. Molecular docking studies highlighted interactions, such as hydrogen bonding, \u03c0\u2013\u03c0 stacking, and hydrophobic interactions, which support the observed inhibitory activity. Density Functional Theory (DFT) studies revealed electronic properties consistent with the observed activity, showing that compounds with smaller energy gaps exhibited higher reactivity. These findings suggest that pyrazole-based thiadiazole\/thiazole hybrids are lead candidates for the development of novel TP inhibitors with anticancer applications.\n                  <\/jats:p>","DOI":"10.1515\/znc-2025-0225","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T16:27:37Z","timestamp":1767889657000},"page":"577-594","source":"Crossref","is-referenced-by-count":2,"title":["Multiparameter optimization of broad-spectrum thymidine phosphorylase inhibition, ADMET properties, molecular docking, and DFT screening of novel pyrazole-based thiadiazole\/thiazole derivatives"],"prefix":"10.1515","volume":"81","author":[{"given":"Reem Nabil","family":"Hassan","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science , King Abdulaziz University (KAU) , P.O. Box\u00a080141 , Jeddah , 21589 , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hina","family":"Sarfraz","sequence":"additional","affiliation":[{"name":"Department of Chemistry , Quaid-i-Azam University Islamabad , 45320 , Islamabad , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-681X","authenticated-orcid":false,"given":"Rafaqat","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Chemistry , Hazara University , Mansehra , Khyber Pakhtunkhwa , 21120 , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Sardar","sequence":"additional","affiliation":[{"name":"Department of Chemistry , Abbottabad University of Science and Technology (AUST) , Abbottabad , 22500 , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9274-2620","authenticated-orcid":false,"given":"Ayaz","family":"Ali Khan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology , University of Malakand Chakdara , 18800 , Dir Lower , KPK , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammena Y.","family":"Binsaleh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy , Princess Nourah bint Abdulrahman University , P.O. Box 84428 , Riyadh , 11671 , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawal","family":"Al-Hoshani","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science , Princess Nourah bint Abdulrahman University , P.O.Box 84428 , Riyadh , 11671 , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maher S.","family":"Alwethynani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences , Shaqra University , Alquwayiyah, Riyadh , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaza N.","family":"Alkhatib","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Collage of Sciences and Arts Khulais , University of Jeddah , Jeddah , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakhria A.","family":"Al-Joufi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy , Jouf University , 72341 , Aljouf , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania Ali El","family":"Hadi Mohamed","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science , Princess Nourah bint Abdulrahman University , P.O.Box 84428 , Riyadh , 11671 , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal F.","family":"Elkhadragy","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science , Princess Nourah bint Abdulrahman University , P.O.Box 84428 , Riyadh , 11671 , Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"2026070715574837016_j_znc-2025-0225_ref_001","doi-asserted-by":"crossref","unstructured":"Vincenzetti, S, Polzonetti, V, Micozzi, D, Pucciarelli, S. 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