{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:08:47Z","timestamp":1787162927861,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,4,16]],"date-time":"2015-04-16T00:00:00Z","timestamp":1429142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A novel series of hybrids was designed and synthesized by combining key elements from farnesylthiosalicylic acid (FTS) and hydroxamic acid. Several 3,7,11\u2010trimethyldodeca\u20102,6,10\u2010trien\u20101\u2010yl) thio)benzamide derivatives, particularly those with branched and linear aliphatic linkers between the hydroxamic zinc binding group (ZBG) and the benzamide core, not only displayed significant antitumor activities against six human cancer cells but also exhibited histone deacetylase (HDAC) inhibitory effects in\u2005vitro. Among them,\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(4\u2010(hydroxyamino)\u20104\u2010oxobutyl)\u20102\u2010(((2\n                    <jats:italic>E<\/jats:italic>\n                    ,6\n                    <jats:italic>E<\/jats:italic>\n                    )\u20103,7,11\u2010trimethyldodeca\u20102,6, 10\u2010trien\u20101\u2010yl)thio)benzamide (\n                    <jats:bold>8\u2009d<\/jats:bold>\n                    ) was the most potent, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 4.9\u20137.6\u2005\u03bc\n                    <jats:sc>M<\/jats:sc>\n                    ; these activities are eight\u2010 to sixteen\u2010fold more potent than FTS and comparable to that of suberoylanilide hydroxamic acid (SAHA). Derivative\n                    <jats:bold>8\u2009d<\/jats:bold>\n                    induced cell cycle arrest in the G0\/G1 phase, inhibited the acetylation of histone H3 and \u03b1\u2010tubulin, and blocked Ras\u2010related signaling pathways in a dose\u2010dependent manner. The improved tumor growth inhibition and cell\u2010cycle arrest in\u2005vitro might result from the dual inhibition. These findings suggest dual inhibitors of Ras\u2010related signaling pathway and HDAC hold promise as therapeutic agents for the treatment of cancer.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.201500019","type":"journal-article","created":{"date-parts":[[2015,4,16]],"date-time":"2015-04-16T13:00:17Z","timestamp":1429189217000},"page":"971-976","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Hybrids from Farnesylthiosalicylic Acid and Hydroxamic Acid as Dual Ras\u2010Related Signaling and Histone Deacetylase (HDAC) Inhibitors: Design, Synthesis and Biological 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