Anticancer activity and biophysical reactivity of copper complexes of 2-(benzo[d][1,3]dioxol-5-ylmethylene)-N-alkylhydrazinecarbothioamides.

A series of copper complexes were synthesized from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) thio-semicarbazones (RHpTSC where R=H, CH3, C2H5 or C6H5 (Ph)). The complexes show interesting variations in geometry depending on the thiosemicarbazone; a dinuclear complex [Cu(HpTSC)Cl]2, a mononuclear complex [Cu(RHpTSC)2Cl2] (R=CH3 or C2H5) and another mononuclear complex [Cu(PhHpTSC)(PhpTSC)Cl] was generated. The complexes bind in a moderately strong fashion to DNA with binding constants on the order of 10(4)M(‒1). They are also strong binders of human serum albumin with binding constants near 10(4) M(‒1). The complexes show good in vitro cytotoxic profiles against two human colon cancer cell lines (HCT-116 and HT29) and two human breast cancer cell lines (MCF-7 and MDA-MB-231) with IC50 values in the low millimolar concentration range.

Half-sandwich ruthenium­arene complexes with thiosemicarbazones: synthesis and biological evaluation of [(η6-p-cymene)Ru(piperonal thiosemicarbazones)Cl]Cl complexes.

The synthesis and characterization of a number of organometallic ruthenium(II) complexes containing a series of bidentate thiosemicarbazone ligands derived from piperonal is reported. The structure of compounds have been confirmed by spectroscopic analysis (IR and NMR) as well as X-ray crystallographic analysis of [(η6-p-cymene)Ru(pPhTSC)Cl]Cl (4) (pPhTSC is piperonal-N(4)-phenylthiosemicarbazone). The interaction of the complexes ([(η6-p-cymene)Ru(pEtTSC)Cl]Cl) (3) (pEtTSC is piperonal-N(4)-ethylthiosemicarbazone) and 4 with calf thymus DNA, human serum albumin (HSA) and pBR322 plasmid DNA were studied by spectroscopic, gel electrophoresis and hydrodynamic methods. The apparent binding constant for the interaction with DNA was determined to be 3.97×10³ M⁻¹ and 4.07×10³ M⁻¹ at 293 K for 3 and 4 respectively. The complexes bind strongly to HSA with binding constants of 2.94×104 M⁻¹ and 12.2×104 M⁻¹ at 296 K for 3 and 4 respectively. The in vitro anticancer activity of 3 and 4 has been evaluated against two human colon cancer cell line (HCT-116 and Caco-2) with IC50 values in the range of 26­150 µM. Both 3 and 4 show good activity as a catalytic inhibitor of human topoisomerase II at concentrations as low as 20 µM. The proficiency of 3 and 4 to act as antibacterial agents was also evaluated against six pathogenic bacterial strains with the best activity seen against Gram-positive strains.

Synthesis and characterization of mixed-ligand diimine-piperonal thiosemicarbazone complexes of ruthenium(II): Biophysical investigations and biological evaluation as anticancer and antibacterial agents.

We have used a novel microwave-assisted method developed in our laboratories to synthesize a series of ruthenium-thiosemicarbazone complexes. The new thiosemicarbazone ligands are derived from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) and the complexes are formulated as [(diimine)(2)Ru(TSC)](PF(6))(2) (where the TSC is the bidentate thiosemicarbazone ligand). The diimine in the complexes is either 2,2'-bipyridine or 1,10-phenanthroline. The complexes have been characterized by spectroscopic means (NMR, IR and UV-Vis) as well as by elemental analysis. We have studied the biophysical characteristics of the complexes by investigating their anti-oxidant ability as well as their ability to disrupt the function of the human topoisomerase II enzyme. The complexes are moderately strong binders of DNA with binding constants of 10(4) M(-1). They are also strong binders of human serum albumin having binding constants on the order of 10(4) M(-1). The complexes show good in vitro anticancer activity against human colon cancer cells, Caco-2 and HCT-116 and indeed show some cytotoxic selectivity for cancer cells. The IC(50) values range from 7 - 159 µM (after 72 h drug incubation). They also have antibacterial activity against Gram-positive strains of pathogenic bacteria with IC(50) values as low as 10 µM; little activity was seen against Gram-negative strains. It has been established that all the compounds are catalytic inhibitors of human topoisomerase II.

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.

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.

Microwave synthesis of mixed ligand diimine-thiosemicarbazone complexes of ruthenium(II): biophysical reactivity and cytotoxicity.

A novel microwave-assisted synthetic method has been used to synthesise a series of mixed ligand ruthenium(II) compounds containing diimine as well as bidentate thiosemicarbazone ligands. The compounds contain the diimine 1,10-phenanthroline (phen) or 2,2'-bipyridine (bpy) and the thiosemicarbazone is derived from 9-anthraldehyde. Based on elemental analyses and spectroscopic data, the compounds are best formulated as [(phen)(2)Ru(thiosemicarbazone)](PF(6))(2) and [(phen)(2)Ru(thiosemicarbazone)](PF(6))(2) where thiosemicarbazone = 9-anthraldehydethiosemicarbazone, 9-anthraldehyde-N(4)-methylthiosemicarbazone, and 9-anthraldehyde-N(4)-ethylthiosemicarbazone. Fluorescence competition studies with ethidium bromide, along with viscometric measurements suggests that the complexes bind calf thymus DNA (CTDNA) relatively strongly via an intercalative mode possibly involving the aromatic rings of the diimine ligands. The complexes show good cytotoxic profiles against MCF-7 and MDA-MB-231 (breast adenocarcinoma) as well as HCT 116 and HT-29 (colorectal carcinoma) cell lines.

Organometallic ruthenium complexes with thiosemicarbazone ligands: Synthesis, structure and cytotoxicity of [(eta-p-cymene)Ru(NS)Cl] (NS = 9-anthraldehyde thiosemicarbazones).

A series of half-sandwich arene-ruthenium complexes of the type [(eta(6)-p-cymene) Ru(thiosemicarbazone)Cl](+) have been synthesized and their biological activity investigated. The first structurally characterized arene-ruthenium half-sandwich complex with a thiosemicarbazone ligand is reported.