Cytotoxicity and topoisomerase I/II inhibition activity of novel 4-aryl/alkyl-1-(piperidin-4-yl)-carbonylthiosemicarbazides and 4-benzoylthiosemicarbazides. (April 2014)

• Record Type: Journal Article
• Authors: Siwek, Agata; Bielawska, Anna; Maciorkowska, Elzbieta; Lepiarczyk, Monika; Bielawski, Krzysztof; Trotsko, Nazar; Wujec, Monika
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 29:Number 2(2014:Apr.)
• Page Start: 243
• Page End: 248
• Publication Date: 2014-04
• Subjects: Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2013.768987
• Languages: English
• ISSNs: 1475-6366

Abstract

<abstract> <title>Abstract</title> <p>A series of eight thiosemicarbazide derivatives was examined for cytotoxicity in breast cancer cell cultures. Among them, 4-benzoylthiosemicarbazides proved to be only slightly less potent than chlorambucil in both MDA-MB-231 and MCF-7 lines. In contrast, 4-aryl/alkylthiosemicarbazides revealed significantly lower cytotoxicity effect. Subsequently, all titled compounds were tested as potential human topoisomerase I and II (topo I and topo II) inhibitors. Mechanistic studies revealed that tested thiosemicarbazides act as both topoisomerase I and topoisomerase II inhibitors. Among them, the best inhibitory activity was found for 4-benzoylthiosemicarbazides (<bold>1</bold> and <bold>2)</bold> with IC₅₀ at 50 µM against topo II.</p> </abstract>