title: 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: Department of Organic Chemistry, Medical University , Lublin , Poland .
authors: Agata
authors: A
authors: Siwek
authors: Anna
authors: A
authors: Bielawska
authors: Elzbieta
authors: E
authors: Maciorkowska
authors: Monika
authors: M
authors: Lepiarczyk
authors: Krzysztof
authors: K
authors: Bielawski
authors: Nazar
authors: N
authors: Trotsko
authors: Monika
authors: M
authors: Wujec
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004278:DNA, Superhelical / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D015394:Molecular Structure; D012663:Semicarbazides / Q000737:chemistry / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D012663:Semicarbazides; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors