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

Abstract

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 (1 and 2) with IC50 at 50 µM against topo II.

• Authors: Agata Siwek, Anna Bielawska, Elzbieta Maciorkowska, Monika Lepiarczyk, Krzysztof Bielawski, Nazar Trotsko, Monika Wujec
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 29 Issue 2 Pg. 243-8 (Apr 2014) ISSN: 1475-6374 [Electronic] England
• PMID: 23432612 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• DNA, Superhelical
• Semicarbazides
• Topoisomerase I Inhibitors
• Topoisomerase II Inhibitors

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Cell Culture Techniques
• Cell Survival (drug effects)
• DNA, Superhelical (drug effects)
• Fibroblasts (drug effects)
• Humans
• Inhibitory Concentration 50
• MCF-7 Cells
• Molecular Structure
• Semicarbazides (chemistry, pharmacology)
• Topoisomerase I Inhibitors (chemistry, pharmacology)
• Topoisomerase II Inhibitors (chemistry, pharmacology)