{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T15:12:07Z","timestamp":1788189127994,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Umm Al-Qura University","award":["25UQU4290670GSSR04"],"award-info":[{"award-number":["25UQU4290670GSSR04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Leukemia is a common cancer that arises in both children and adults when bone marrow\u2019s hematopoietic stem cells proliferate unrestrained because of anomalies in normal cell regulatory systems. The present study focused on biological evaluation of oxazole-based oxadiazole scaffolds to evaluate the anti-proliferative effect on leukemic cancer cell lines. Methods: All novel oxazole-based oxadiazole scaffolds were synthesized and structurally characterized via 13C NMR, 1H NMR, and HREI-MS. In order to identify an efficient anti-leukemia agent, the biological profiles of each compound were evaluated in comparison to the reference drug, Etoposide (IC50 = 10.50 and 15.20 \u03bcM). Results: Analog 6 substituted with p-CF3 at phenyl ring was identified with excellent inhibition against the HL-60 and PLB-985 cancer cell lines, with IC50 of 8.50 and 12.50 \u03bcM. Through hydrogen bond formation, the trifluoromethyl moiety of analog 6 interacts with target tyrosine kinase enzyme (PDB-ID:4CSV). The interactive character of active ligands with target enzyme was demonstrated by molecular docking. The rate of inhibition in contrast with the drug concentration was also tested to check the inhibition percentage and inhibitor type via enzyme kinetics. Furthermore, the enzyme\u2013ligand complex was also investigated via MD simulation along with pharmacophore modeling. DFT calculations were used to estimate the lead compounds\u2019 relative stability and reactivity. According to ADMET investigation, there is safe toxicological profile for these compounds. Conclusions: The current study suggests that the potent compounds have significant anti-proliferative potential, and with further in vivo validation, hold promise for future optimization as potential leukemia treatments.<\/jats:p>","DOI":"10.3390\/ph18050625","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T10:42:09Z","timestamp":1745577729000},"page":"625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Anti-Leukemic Profiling of Oxazole-Linked Oxadiazole Derivatives: A Computational and Kinetic Approach"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5294-2193","authenticated-orcid":false,"given":"Manal M.","family":"Khowdiary","sequence":"first","affiliation":[{"name":"Department of Chemistry, Facullty of Applied Science, University College-Al Leith, University of Umm Al-Qura, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-0954","authenticated-orcid":false,"given":"Shoaib","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayyiaba","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wajid","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Hazara University, Mansehra 21300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azam","family":"Hayat","sequence":"additional","affiliation":[{"name":"Department of MLT, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, 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 21300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehad A. L.","family":"Shaaer","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Facullty of Applied Science, University College-Al Leith, University of Umm Al-Qura, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamdy","family":"Kashtoh","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s11468-020-01334-0","article-title":"Mono-rectangular core photonic crystal fiber (MRC-PCF) for skin and blood cancer detection","volume":"16","author":"Eid","year":"2021","journal-title":"Plasmonics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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