Synthesis and characterization of complexes of p-isopropyl benzaldehyde and methyl 2-pyridyl ketone thiosemicarbazones with Zn(II) and Cd(II) metallic centers. Cytotoxic activity and induction of apoptosis in Pam-ras cells (original) (raw)
Related papers
J Inorg Biochem, 1999
The reaction of [ReOCl 3 (PPh 3 ) 2 ] with N, N-bis(2-mercaptoethyl)benzylamine and 4bromobenzenethiol allowed for the isolation of [ReO{η 3 -(SCH 2 CH 2 ) 2 N(CH 2 C 6 H 5 )}-(η 1 -C 6 H 4 Br-4-S)] (1). The reaction of [ReOCl 3 (PPh 3 ) 2 ] with [(HSCH 2 CH 2 ) 2 N(CH 2 C 5 H 4 N)] and the appropriate thiol in chloroform treated with triethylamine has led to the isolation of a series of neutral rhenium complexes of the type [ReO{η 3 -(SCH 2 CH 2 ) 2 N(CH 2 C 5 H 4 N)}(η 1 -C 6 H 4 X-4-S)] (X = Br (2), Cl (3), F (4), and OCH 3 (5)) and [ReO{η 3 -(SCH 2 CH 2 ) 2 N(CH 2 C 5 H 4 N)}(η 1 -C 6 H 4 OCH 3 -4-CH 2 S)] (6). Likewise, under similar reaction conditions, the use of the related tridentate ligand, [(HSCH 2 CH 2 ) 2 N(CH 2 CH 2 C 5 H 4 N)], has led to the isolation of a series of rhenium complexes of the type [ReO{η 3 -(SCH 2 CH 2 ) 2 N(CH 2 CH 2 C 5 H 4 N)}(η 1 -C 6 H 4 X-4-S)] (X=Br , Cl (8), OCH 3 (9)), as well as [ReO{η 3 -(SCH 2 CH 2 ) 2 N(CH 2 CH 2 C 5 H 4 N)}(η 1 -C 6 H 4 Cl-4-CH 2 S)]·0.5CH 3 (CH 2 ) 4 CH 3 (10). These compounds are extensions of the '3+1' approach to the synthesis of materials with the {MO} 3+ core (M=Tc and Re), which have applications in nuclear medicine. The ligands chosen allow systematic exploration of the consequences of para-substitution on the monodentate thiolate ligand [S] and of derivatization of the substituent R on the tridentate aminodithiol ligand [SNS] of the type (HSCH 2 CH 2 ) 2 NR. Such modifications can influence lipophilicity, charge, size and molecular weight of the complex and consequently the biodistribution.
Rhenium mixed-ligand complexes with S,N,S-tridentate thiosemicarbazone/thiosemicarbazide ligands
Dalton Transactions, 2013
Rhenium(V) complexes containing tridentate thiosemicarbazones/thiosemicarbazides (H 2 L1) derived from N-[N',N'-dialkylamino(thiocarbonyl)]benzimidoyl chlorides with 4,4-dialkylthiosemicarbazides have been synthesized by ligand-exchange reactions starting from [ReOCl(L1)]. The chlorido ligand of [ReOCl-(L1)] (4) is readily replaced and reactions with ammonium thiocyanate or potassium cyanide give [ReO-(NCS)(L1)] (6) and [ReO(CN)(L1)] (7), respectively. The reaction of (NBu 4)[ReOCl 4 ] with H 2 L1 and two equivalents of ammonium thiocyanate, however, gives in a one-pot reaction [ReO(NCS) 2 (HL1)] (8), in which the pro-ligand H 2 L1 is only singly deprotonated. An oxo-bridged, dimeric nitridorhenium(V) compound of the composition [{ReN(HL1)} 2 O] (11) is obtained from a reaction of (NBu 4)[ReOCl 4 ], H 2 L1 and sodium azide. The six-coordinate complexes [ReO(L1)(Ph 2 btu)] (12), where HPh 2 btu is N,N-diphenyl-N'benzoylthiourea, can be obtained by treatment of [ReOCl(L1)] with HPh 2 btu in the presence of NEt 3. Studies of the antiproliferative effects of the [ReOX(L1)] system (X = Cl − , NCS − or CN −) on breast cancer cells show that the lability of a monodentate ligand seems to play a key role in the cytotoxic activity of the metal complexes, while the substitution of this ligand by the chelating ligand Ph 2 btu − completely terminates the cytotoxicity. Chart 1 Rhenium complexes with thiosemicarbazones (for details see ref. 14-19).
Keywords: Ruthenium(II) carbonyl complexes DNA/BSA interaction In vitro anticancer activity a b s t r a c t A serious of new dissymmetric ruthenium(II) carbonyl complexes of the type [Ru(CO)(EPh 3)(L1e2)] (1e4), [E ¼ P or As; L1 ¼ N 4-(2-Hydroxy-5-chlorobenzylidene)-2-amino-5-chlorobenzophenone thio-semicarbazone; L2 ¼ N 4-(2-Hydroxynaphthalene-1-carbaldehyde)-2-amino-5-chlorobenzophenone thiosemicarbazone] have been synthesized and characterized by several spectroscopic studies. The molecular structure of the ligand L1 and the ruthenium(II) carbonyl complexes (2, 4) have been analyzed by single crystal X-ray studies, and found that the ruthenium(II) complexes possess a distorted octa-hedral geometry. The DNA binding studies such as emissive titration, Ethidium bromide/Methylene blue (EB/MB) displacement assay and viscometry measurements revealed that the ruthenium(II) complexes bound with calf thymus DNA through intercalative mode with relatively high binding constant values. Further, the interactions of the complexes with bovine serum albumin (BSA) were also investigated using fluorescence spectroscopic methods, which showed that the new complexes could bind strongly with BSA. The complexes (1e4) were tested for DNA and BSA cleavage activities, and the results showed that the complexes exhibited good cleavage properties. In addition, the newly synthesized ruthenium(II) complexes possess better in vitro cytotoxic activities against various cell lines (MCF-7, Hop62, MDA-MB-435) and AO/EB staining method showed that these complexes induced apoptosis of MCF-7 cell lines.
Dissymmetric thiosemicarbazone ligands containing substituted.pdf
A serious of new dissymmetric ruthenium(II) carbonyl complexes of the type [Ru(CO)(EPh 3 )(L1e2)] (1e4), [E ¼ P or As; L1 ¼ N 4 -(2-Hydroxy-5-chlorobenzylidene)-2-amino-5-chlorobenzophenone thiosemicarbazone; L2 ¼ N 4 -(2-Hydroxynaphthalene-1-carbaldehyde)-2-amino-5-chlorobenzophenone thiosemicarbazone] have been synthesized and characterized by several spectroscopic studies. The molecular structure of the ligand L1 and the ruthenium(II) carbonyl complexes (2, 4) have been analyzed by single crystal X-ray studies, and found that the ruthenium(II) complexes possess a distorted octahedral geometry. The DNA binding studies such as emissive titration, Ethidium bromide/Methylene blue (EB/MB) displacement assay and viscometry measurements revealed that the ruthenium(II) complexes bound with calf thymus DNA through intercalative mode with relatively high binding constant values. Further, the interactions of the complexes with bovine serum albumin (BSA) were also investigated using fluorescence spectroscopic methods, which showed that the new complexes could bind strongly with BSA. The complexes (1e4) were tested for DNA and BSA cleavage activities, and the results showed that the complexes exhibited good cleavage properties. In addition, the newly synthesized ruthenium(II) complexes possess better in vitro cytotoxic activities against various cell lines (MCF-7, Hop62, MDA-MB-435) and AO/EB staining method showed that these complexes induced apoptosis of MCF-7 cell lines.
Polyhedron, 2015
The potentially tetradentate benzamidine/thiosemicarbazone ligand, Et 2 N-(C=S)-NH-C(Ph)=N-(o-C 4 H 6)-C(Me)=N-NH-(C=S)-NH-Me (H 2 L) readily reacts with Ni(CH 3 COO) 2 , [PdCl 2 (CH 3 CN) 2 ], [PtCl 2 (PPh 3) 2 ] and (NBu 4)[ReOCl 4 ] under formation of complexes of the compositions [M(L)] (M= Ni (1), Pd (2), Pt (3)) and [ReO(L)(OMe)] (4). In all complexes, H 2 L is doubly deprotonated and bonded to the central meal ion via its N 2 S 2 donor set. Complexes 1, 2 and 3 have distorted square-planar coordination spheres, while the rhenium compound 4 is an octahedral trans oxido/methoxido complex. The H 2 L proligand shows a medium cytotoxicity with an IC 50 value of 21.1 M. While the rhenium complex 4 exhibits a stronger antiproliferative effect (IC 50 = 5.52 M), the nickel, palladium and platinum complexes are almost inactive.
Interdisciplinary Journal of Chemistry, 2016
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 [(η 6-p-cymene)Ru(dmabTSC)Cl]PF 6 , [(η 6-benzene) Ru(dmabTSC)Cl]PF 6 (arene complexes), and [([9]aneS 3 (dmabTSC)Cl]PF 6 (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 calfthymus DNA with binding constants on the order of 10 5 M-1. In addition they all bind strongly to human serum albumin with binding constants between 10 5 and 10 6 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.
Rhenium(I) complexes with aliphatic Schiff bases appended to bio-active moieties
Inorganic Chemistry Communications, 2017
Novel facial tricarbonylrhenium(I) complexes, fac-[Re(urca)2(CO)3Cl] (1) and fac-[Re(bzta)(CO)3Cl] (2) were isolated from the coordination reactions of 5-((5-hydroxypentylimino)methyl)uracil (urca) and 2-((5hydroxypentylimino)methyl)benzothiazole (bzta) with [Re(CO)5Cl], respectively. Spectral characterization of metal complexes 1 and 2 were supported by their X-ray crystal structures. DNA interactions were assessed via UV-Vis calf-thymus (CT)-DNA binding titrations and gel electrophoresis. Redox properties of the metal complexes were probed using voltammetry.
ChemMedChem
Herein we illustrate the formation and characterization of new paramagnetic ruthenium compounds, trans-P-[RuCl(PPh 3) 2 (pmt)]Cl (1) (Hpmt = 1-((pyridin-2-yl)methylene)thiosemicarbazide), trans-P-[RuCl(PPh 3) 2 (tmc)]Cl (2) (Htmc = 1-((thiophen-2-yl)methylene)thiosemicarbazide) and a diamagnetic ruthenium complex, cis-Cl, trans-P-[RuCl 2 (PPh 3) 2 (btm)] (3) (btm = 2-((5-hydroxypentylimino)methyl)benzothiazole). Agarose gel electrophoresis experiments of the metal compounds illustrated dose-dependent binding to gDNA by 1-3, while methylene blue competition assays suggested that 1 and 2 are also DNA intercalators. Assessment of the effects of the compounds on topoisomerase function indicated that 1-3 are capable of inhibiting topoisomerase I activity in terms of the ability to nick supercoiled plasmid DNA. The cytotoxic activities of the metal complexes were determined against a range of cancer cell lines versus a nontumorigenic control cell line, and the complexes were, in general, more cytotoxic towards the cancer cells, displaying IC 50 values in the low micromolar range. Time-dependent stability studies showed that in the presence of strong nucleophilic species (such as DMSO), the chloride co-ligands of 1-3 are rapidly substituted by the former as proven by the suppression of the substitution reactions in the presence of an excess amount of chloride ions. The metal complexes are significantly stable in both DCM and an aqueous phosphate buffer containing 2 % DMSO.
Journal of Inorganic Biochemistry, 2011
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 [(η 6 -p-cymene)Ru(pPhTSC)Cl]Cl (4) (pPhTSC is piperonal-N(4)-phenylthiosemicarbazone). The interaction of the complexes ([(η 6 -pcymene)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 × 10 3 M −1 and 4.07 × 10 3 M −1 at 293 K for 3 and 4 respectively. The complexes bind strongly to HSA with binding constants of 2.94 × 10 4 M −1 and 12.2 × 10 4 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 with IC 50 values in the range 26 -150 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.