Organometallic Ruthenium Complexes of Novel Thiosemicarbazones

We present the preliminary results of a study of two novel thiosemicarbazones (TSCs) and theirruthenium complexes. The TSCs were prepared by refluxing thiosemicarbazide with 9-anthraldehyde or benzanthrone in ethanol for 3 hours. The metal complex of each ligand (complex I =[(r|6 -C6H6 )Ru(9-ant-TSC )(C1)]C1 and complex II= [(r|6 -C6H6 )Ru(benz-TSC)(Cl)]Cl) was prepared by refluxing the appropriate TSC with [(r|6 -C6H6 )RuCl 2 ] r The compounds were characterized using infrared, ultraviolet-visible, and NMRspectroscopy. Two different methods, the disk diffusion test and luminometry, were used to test the compounds against a variety of different bacterial strains for antibacterial activity. The most optimistic results were obtained for the 9-ant-TSC ligand, especially in relation to activity against Gram (+) bacteria. The metal complexes showed no measurable activity and further biological testing of the metal complexes is currently being conducted

Cytotoxic gallium complexes containing thiosemicarbazones derived from 9-anthraldehyde: Molecular docking with biomolecules

We have synthesized a trio of gallium complexes bearing 9-anthraldehyde thiosemicarbazones. The complexes were assessed for their anticancer activity and their biophysical reactivity was also investigated. The three complexes displayed good cytotoxic profiles against two human colon cancer cell lines, HCT-116 and Caco-2. The IC50 ranged from 4.7 to 44.1 μM with the complex having an unsubstituted amino group on the thiosemicarbazone being the most active. This particular complex also showed a high therapeutic index. All three complexes bind strongly to DNA via intercalation with binding constants ranging from 7.46 × 104 M−1 to 3.25 × 105 M−1. The strength of the binding cannot be directly related to the level of anticancer activity. The complexes also bind strongly to human serum albumin with binding constants on the order of 104–105 M−1 as well. The complexes act as chemical nucleases as evidenced by their ability to cleave pBR322 plasmid DNA. The binding constants along with the cleavage results may suggest that the extent of DNA interaction is not directly correlated with anticancer activity. The results of docking studies with DNA, ribonucleotide reductase and human serum albumin, however showed that the complex with the best biological activity had the largest binding constant to DNA

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) thiosemicarbazones (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 104 M− 1. They are also strong binders of human serum albumin with binding constants near 104 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

Organometallic ruthenium complexes with thiosemicarbazone ligands: Synthesis, structure and cytotoxicity of [(η\u3csup\u3e6\u3c/sup\u3e-p-cymene)Ru(NS)Cl]\u3csup\u3e+\u3c/sup\u3e (NS = 9-anthraldehyde thiosemicarbazones)

A series of half-sandwich arene ruthenium complexes containing bidentate thiosemicarbazone ligands have been synthesized and their biological activity investigated. The compounds have the general formula [(6-p-cymene)Ru(R-ATSC)Cl]X (ATSC = 9-anthraldehyde thiosemicarbazone and R = H, CH3 and C6H5). The crystal structure of [(6-p-cymene) Ru(MeATSC)Cl]Cl have been determined and represents the first structurally characterized arene–ruthenium half-sandwich complex with a thiosemicarbazone ligand. 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. [Refer to PDF for graphical abstract

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)2Ru(TSC)](PF6)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 104 M−1. They are also strong binders of human serum albumin having binding constants on the order of 104 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 IC50 values range from 7 to 159 μM (after 72 h drug incubation). They also have antibacterial activity against Gram-positive strains of pathogenic bacteria with IC50 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

Anticancer, Biophysical and Computational Investigations of Half-Sandwich Ruthenium(II) Thiosemicarbazone Complexes: The Effect of Arene \u3ci\u3eVersus\u3c/i\u3e Thiacrown Face-Cap

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h6-p-cymene)Ru(dmabTSC)Cl]PF6, [(h6-benzene)Ru(dmabTSC)Cl]PF6 (arene complexes), and [([9]aneS3(dmabTSC)Cl]PF6 (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 105 M-1. In addition they all bind strongly to human serum albumin with binding constants between 105 and 106 M-1. There appears to be a single binding site on the protein for these complexes. A computational investigation of these complexes and their hydrolysis products was carried out by molecular docking with DNA and topoisomerase II. From this analysis it is noted that the type of face-capping ligand had different effects on the two macromolecules. It is therefore noted that the knowledge gained from this study will be useful in identifying the type of complexes in this class that show useful metallodrug potential

Synthesis, Characterisation, and Preliminary In Vitro Studies of Vanadium(IV) Complexes with a Schiff Base and Thiosemicarbazones as Mixed Ligands

[VO(sal‐L‐tryp)(H2O)] (1, sal‐L‐tryp = N‐salicylidene‐L‐tryptophanate) was used as a precursor to produce the new complexes [VO(sal‐L‐tryp)(MeATSC)]·1.5C2H5OH [2, MeATSC = 9‐Anthraldehyde‐N(4)‐methylthiosemicarbazone], [VO(sal‐L‐tryp)(N‐ethhymethohcarbthio)]·H2O [3, N‐ethhymethohcarbthio = (E)‐N‐ethyl‐2‐(4‐hydroxy‐3‐methoxybenzylidene)hydrazinecarbothioamide] and [VO(sal‐L‐tryp)(acetylethTSC)]·C2H5OH {4, acetylethTSC = (E)‐N‐ethyl‐2‐[1‐(thiazol‐2‐yl)ethylidene]hydrazinecarbothioamide} by reaction with the respective thiosemicarbazone. The chemical and structural properties of these ligands and complexes were characterised by elemental analysis, ESI‐MS, FTIR, UV/Vis, ESR and 1H and 13C NMR spectroscopy and X‐ray crystallography. Dimethyl sulfoxide (DMSO) and [D6]DMSO solutions of 1–4 were oxidised in air to produce vanadium(V) species, which were verified by ESI‐MS and 51V NMR spectroscopy. The anticancer properties of 2–4 were examined with three colon cancer cell lines, HTC‐116, Caco‐2 and HT‐29, and noncancerous colonic myofibroblasts, CCD18‐Co. Compounds 2–3 exhibited less inhibitory effects in the CCD‐18Co cells, which indicates a possible cytotoxic selectivity towards colon cancer cells. In general, compounds that exhibit antiproliferative activity to cancer cells but do not affect noncancerous cells may have a potential in chemotherapy

Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand

In this study, 9-anthraldehyde-N(4)-methylthiosemicarbazone (MeATSC) 1 and [Co(phen)(OCO)]Cl·6HO 2 (where phen = 1,10-phenanthroline) were synthesized. [Co(phen)(OCO)]Cl·6HO 2 was used to produce anhydrous [Co(phen)(HO)](NO)3. Subsequently, anhydrous [Co(phen)(HO)](NO)3 was reacted with MeATSC 1 to produce [Co(phen)(MeATSC)](NO)·1.5HO·CHOH 4. The ligand, MeATSC 1 and all complexes were characterized by elemental analysis, FT IR, UV-visible, and multinuclear NMR (H, C, and Co) spectroscopy, along with HRMS, and conductivity measurements, where appropriate. Interactions of MeATSC 1 and complex 4 with calf thymus DNA (ctDNA) were investigated by carrying out UV-visible spectrophotometric studies. UV-visible spectrophotometric studies revealed weak interactions between ctDNA and the analytes, MeATSC 1 and complex 4 (K = 8.1 × 10 and 1.6 × 10 M, respectively). Topoisomerase inhibition assays and cleavage studies proved that complex 4 was an efficient catalytic inhibitor of human topoisomerases I and IIα. Based upon the results obtained from the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay on 4T1-luc metastatic mammary breast cancer cells (IC = 34.4 ± 5.2 μM when compared to IC = 13.75 ± 1.08 μM for the control, cisplatin), further investigations into the molecular events initiated by exposure to complex 4 were investigated. Studies have shown that complex 4 activated both the apoptotic and autophagic signaling pathways in addition to causing dissipation of the mitochondrial membrane potential (ΔΨ). Furthermore, activation of cysteine-aspartic proteases3 (caspase 3) in a time- and concentration-dependent manner coupled with the ΔΨ, studies implicated the intrinsic apoptotic pathway as the major regulator of cell death mechanism

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)2Ru(thiosemicarbazone)](PF6)2 and [(phen)2Ru(thiosemicarbazone)](PF6)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