{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T21:56:24Z","timestamp":1790546184617,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Vorinostat, a hydroxamic acid\u2010based histone deacetylase (HDAC) inhibitor approved for cutaneous T\u2010cell lymphoma, exhibits broad\u2010spectrum anticancer activity. However, its clinical application is limited by poor permeability and rapid metabolism, which result in a short half\u2010life and consequently poor therapeutic efficacy. To address these constraints, we synthesized a series of lipid\u2010vorinostat conjugates (3a\u2010d) through acylation of vorinostat with short\u2010chain fatty acid chloride derivatives (2a\u2010d). The chemical structures and purity of the conjugates (3a\u2010d) were confirmed using NMR, HRMS, and HPLC analyses. Among these derivatives, compound 3d (3,5,5\u2010Trimethylhexanoyl\u2010Vorinostat) demonstrated improved cytotoxicity against A549 and 4T1 carcinoma cells. Mechanistic insight revealed that the compound 3d induced higher levels of caspase\u20103\/7 activation, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) loss compared with vorinostat, suggesting enhanced apoptosis. The cell scratch assay demonstrated that 3d markedly inhibited cell migration as compared with vorinostat. Furthermore, in silico ADMET profiling predicted enhanced membrane permeability of the compound 3d as compared to vorinostat. The in vitro plasma stability revealed time\u2010dependent hydrolysis of compound 3d to release active vorinostat, supporting its prodrug behavior. Collectively, these findings suggest lipid conjugation as a promising prodrug strategy to modulate the biological and physicochemical properties of vorinostat.<\/jats:p>","DOI":"10.1002\/cbdv.71726","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:56:05Z","timestamp":1790538965000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Biological Evaluation of a Lipophilic Vorinostat Prodrug"],"prefix":"10.1002","volume":"23","author":[{"given":"Navneet","family":"Thakur","sequence":"first","affiliation":[{"name":"Formulation Laboratory, Dietetics and Nutrition Technology Division CSIR\u2010Institute of Himalayan Bioresource Technology Palampur Himachal Pradesh India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad 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