Synthesis and Biological Evaluation of Novel 4‐(2‐Fluorophenoxy)‐2‐(1H‐tetrazol‐1‐yl)pyridines Bearing Semicarbazone Moieties as Potent Antitumor Agents. Issue 11 (1st October 2013)

• Record Type: Journal Article
• Authors: Qin, Mingze; Liao, Weike; Xu, Chen; Fu, Baolin; Ren, Jianguo; Gu, Yucheng; Gong, Ping
• Is Part Of: Archiv der Pharmazie. Volume 346:Issue 11(2013:Nov.)
• Page Start: 840
• Page End: 850
• Publication Date: 2013-10-01
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201300188
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201300188-sec-0001" sec-type="section"> <p>A series of 4‐(2‐fluorophenoxy)‐2‐(1<italic>H</italic>‐tetrazol‐1‐yl)pyridines bearing semicarbazone moieties were synthesized and evaluated for their <italic>in vitro</italic> antitumor potency. Some of the compounds (<bold>10b</bold>, <bold>10c</bold>, <bold>10e</bold>–<bold>10h</bold>, <bold>10m</bold>–<bold>10p</bold>, <bold>10r</bold>, and <bold>11b</bold>) exhibited moderate to excellent antitumor activity as compared to sorafenib and PAC‐1, as well as low levels of toxicity toward the human fetal lung fibroblast cell line WI‐38. The most promising compound <bold>10p</bold> (IC₅₀ = 0.08, 0.36, 0.97 µM) was 45.1‐, 6.1‐, and 2.4‐fold more active than sorafenib (IC₅₀ = 3.61, 2.19, 2.32 µM), and 17, 3.2, and 2.9 times better than PAC‐1 (IC₅₀ = 1.36, 1.17, 2.83 µM) against three cancer cell lines (HT‐29, H460, and MKN‐45), respectively. In addition, further studies examining enzymatic activity suggested that the marked pharmacological activity observed might be ascribed to an inhibitory action against CRAf kinase.</p> </sec> </abstract>