title: Synthesis and structure of [(η(6)-p-cymene)Ru(2-anthracen-9-ylmethylene-N-ethylhydrazinecarbothioamide)Cl]Cl; biological evaluation, topoisomerase II inhibition and reaction with DNA and human serum albumin.
abstract: We have synthesized and evaluated the biological properties of a compound of the type [η(6)-p-cymene)Ru(EtATSC)Cl]Cl (1) where EtATSC = 2-anthracen-9-ylmethylene-N-ethylhydrazinecarbothioamide, a thiosemicarbazone. The complex has been characterized by elemental analysis, spectroscopically (NMR, UV-Vis, and IR) and structurally by XRD. The in vitro anticancer activity of 1 has been evaluated against two human colon cancer cell lines. The IC(50) value for activity against HCT-116 was 224 ± 7 μM and 205 ± 5 μM against the Caco-2 cell line. The proficiency of 1 as an antibacterial agent was also evaluated against six bacterial strains. The minimum inhibitory concentration for Bacillus cereus was determined to be 5 μM and for Enterococcus faecalis it was 20 μM. At the maximum concentration tested the complex showed no activity against the Gram-negative strains. The complex binds strongly to human serum albumin with a binding constant of 1.37 ± 0.02 M(-1) at 308 K on a single binding site. It is also a strong binder to DNA with an apparent binding constant of 2.82 × 10(5) M(-1) at 308 K. 1 shows very good activity as a catalytic inhibitor of human topoisomerase II at concentrations as low as 20 μM.
authors.affiliation: Science Division, Lyon College, Batesville, AR 72501, USA. floyd.beckford@lyon.edu
authors.forename: Floyd
authors.initials: F
authors.lastname: Beckford
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Thessing
authors.forename: Jason
authors.initials: J
authors.lastname: Woods
authors.forename: Jacob
authors.initials: J
authors.lastname: Didion
authors.forename: Nikolay
authors.initials: N
authors.lastname: Gerasimchuk
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez-Sarrias
authors.forename: Navindra P
authors.initials: NP
authors.lastname: Seeram
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001409:Bacillus cereus / Q000187:drug effects / Q000254:growth & development; D055162:Biocatalysis / Q000187:drug effects; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D000081007:Cymenes; D004247:DNA / Q000737:chemistry*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D013293:Enterococcus faecalis / Q000187:drug effects / Q000254:growth & development; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000737:chemistry*; D013997:Time Factors; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C561545:(eta6-p-cymene)ruthenium(2-anthracen-9-ylmethylene-N-ethylhydrazinecarbothioamide); D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D000081007:Cymenes; D009942:Organometallic Compounds; D012709:Serum Albumin; D013882:Thiosemicarbazones; D059005:Topoisomerase II Inhibitors; D012428:Ruthenium; D004247:DNA; D004250:DNA Topoisomerases, Type II