title: Synthesis, cytotoxic activity and DNA-interaction studies of novel anthraquinone-thiosemicarbazones with tautomerizable methylene group.
abstract: A series of novel anthraquinone-thiosemicarbazone derivatives in a tautomerizable keto-imine form was synthesized and tested for their in vitro cytotoxic activity against human cancer cells (HeLa, MDA-MB-361, MDA-MB-453, K562, A549) and human normal MRC-5 cells. Several compounds efficiently inhibited cancer cell growth at micromolar concentrations, especially against K562 and HeLa cells. As determined by flow cytometric analysis, anthraquinone-thiosemicarbazone caused significant increase in the number of sub-G1 phase of HeLa cells and apoptosis in a concentration-dependent manner. Also, inhibition of caspase-3, -8, and -9 with specific caspase inhibitors reduced the apoptosis mediated by the tested compounds in HeLa cells. All anthraquinone-thiosemicarbazones exhibit calf thymus DNA-binding activity, but no cleavage of plasmid DNA was observed.
authors: Department of Chemistry, University of Kragujevac, R. Domanovica 12, 34000 Kragujevac, Serbia.
authors: Violeta
authors: V
authors: Marković
authors: Ana
authors: A
authors: Janićijević
authors: Tatjana
authors: T
authors: Stanojković
authors: Branka
authors: B
authors: Kolundžija
authors: Dušan
authors: D
authors: Sladić
authors: Miroslava
authors: M
authors: Vujčić
authors: Barbara
authors: B
authors: Janović
authors: Ljubinka
authors: L
authors: Joksović
authors: Predrag T
authors: PT
authors: Djurdjević
authors: Nina
authors: N
authors: Todorović
authors: Snežana
authors: S
authors: Trifunović
authors: Milan D
authors: MD
authors: Joksović
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites / Q000187:drug effects; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D000975:Antioxidants; D013882:Thiosemicarbazones; D004247:DNA; C427203:calf thymus DNA; D008697:Methane