title: New spiro tria(thia)zolidine-acridines as topoisomerase inhibitors, DNA binders and cytostatic compounds.
abstract: Three new diphenylsubstituted spirotriazolidine- and thiazolidinone-acridines were prepared and their interaction with calf thymus DNA investigated with UV-vis, fluorescence, circular dichroism spectroscopy and viscometry. The binding constants K were estimated to range from 0.34 to 0.93 × 10(4) M(-1). UV-vis, fluorescence and circular dichroism measurements indicated that the compounds act as effective DNA-interacting agents. Electrophoretic separation proved that ligands inhibited topoisomerase I and II. The biological activity of compounds 3, 5 &6 at several different concentrations (10, 20 and 50 μM) was evaluated both 48 h and 72 h following their addition to HL-60 cancer cells. The results were analysed using various different techniques (MMP detection, changes in metabolic activity/viability and analysis of cell cycle distribution). Acridine was also used as the positive control in these assays. The results from MMP analysis demonstrate the strong effect of 3-diphenylamino-2-(acridin-9-yl)imino-1,3-thiazolidin-4-one (5) on mitochondrial physiology. Cell viability analysis showed that acridine derivatives 3 and 6 were less effective than derivative 5 and the acridine control.
authors: Department of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Košice, Košice, Slovak Republic.
authors: Othman M
authors: OM
authors: Salem
authors: Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Košice, Košice, Slovak Republic.
authors: Mária
authors: M
authors: Vilková
authors: Department of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Košice, Košice, Slovak Republic; Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
authors: Jana
authors: J
authors: Janočková
authors: Department of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, Košice, Slovak Republic.
authors: Rastislav
authors: R
authors: Jendželovský
authors: Department of Cellular Biology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University in Košice, Košice, Slovak Republic.
authors: Peter
authors: P
authors: Fedoročko
authors: Department of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Košice, Košice, Slovak Republic.
authors: Eva
authors: E
authors: Žilecká
authors: Department of Biophysics, Faculty of Science, Palacky University in Olomouc, Olomouc, Czech Republic.
authors: Jana
authors: J
authors: Kašpárková
authors: Department of Biophysics, Faculty of Science, Palacky University in Olomouc, Olomouc, Czech Republic.
authors: Viktor
authors: V
authors: Brabec
authors: Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Košice, Košice, Slovak Republic.
authors: Ján
authors: J
authors: Imrich
authors: Department of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Šafárik University in Košice, Košice, Slovak Republic; Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic. Electronic address: maria.kozurkova@upjs.sk.
authors: Mária
authors: M
authors: Kožurková
mesh_terms: D000166:Acridines / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D059003:Topoisomerase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D013141:Spiro Compounds; D059003:Topoisomerase Inhibitors; D004247:DNA; C427203:calf thymus DNA; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II
keywords: DNA-binding; HL-60 cells; Spiroacridine derivatives; Topoisomerases I and II