GENOTOXIC EVALUATION OF NEWLY SYNTHESIZED ORGANOMETALLIC COMPOUNDS OF TIN (original) (raw)
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Applied Organometallic Chemistry, 2000
- are potent cytotoxic agents against suspended tumors, producing cell death in several tissue culture lines; for example, all were effective against murine L1210 lymphoid leukemia, and all except 5 against murine P388 lymphocytic growth. Human leukemic growth is also retarded since 1-4 were effective against Tmolt 3 cell leukemia, all except 4 against Tmolt 4 leukemia, and 1, 2, and 5 against HI-60 leukemia. Cytotoxicity was found towards HuT-8 lymphoma, THP-1 acute monocytic leukemia and suspended HeLa-S 3 uterine carcinoma. Some but not all of the complexes were active against Sk-2 melanoma and Mcf-7 breast effusion growth. Mode-of-action studies in P388 lymphocytic leukemia cells showed that de novo purine synthesis was inhibited; this inhibition reduces DNA and RNA syntheses. Purine synthesis was reduced by compounds 3 and 4 at the regulatory enzymes, i.e. phosphoribosyl pyrophosphate (PRPP) amidotransferase and dihydrofolate reductase. The agents lowered d[ATP] and d[CTP] pools, further reducing DNA synthesis. The complexes afforded DNA fragmentation leading to apoptosis, but this was not by a mechanism of nucleoside alkylation, intercalation between base-pairs or cross-linking of the DNA strands.
Tin(IV) Cyanoximates: Synthesis, Characterization, and Cytotoxicity †
Inorganic Chemistry, 2007
In recent years, numerous organotin(IV) derivatives have exhibited remarkable cytotoxicity against several types of cancer. However, the properties of the cyanoxime-containing organotin(IV) complexes are unknown. Previously, it has been shown that cyanoximes displayed an interesting spectrum of biological activity ranging from growth-regulation to antimicrobial and pesticide detoxification actions. The work presented here attempts to combine the useful properties of both groups of compounds and investigate the likely antiproliferating activity of the new substances. A series of 19 organotin(IV) complexes, with nine different cyanoxime ligands, were anaerobically prepared by means of the heterogeneous metathesis reaction between the respective organotin(IV) halides (Cl, Br) and ML (M ) Ag, Tl; L ) cyanoximate anion), using an ultrasound in the CH 3 CN at room temperature. The compounds were characterized using spectroscopic methods (UV−visible, IR, 1 H, 13 C NMR, 119 Sn Mössbauer) and X-ray analysis. The crystal structures of the complexes revealed the formation of two types of tin(IV) cyanoximates: mononuclear five-coordinated compounds of R 4 -x SnL x composition (R ) Me, Et, n-Bu, Ph; x ) 1, 2; L ) cyanoximate anion), and the tetranuclear R 8 Sn 4 -(OH) 2 O 2 L 2 species (R ) n-Bu, Ph). The latter complex contains a planar [Sn 4 (OH) 2 O 2 ] 2core, consisting of three adjacent rhombs with bridging oxo and hydroxo groups. The tin(IV) atoms are five-coordinated and have distorted trigonal-pyramidal surrounding. This is the first instance when the organic anions were found to act as monodentate O-bound planar oxime ligands. All of the compounds were studied in vitro for antiproliferating activity, using human cervical cancer HeLa and WiDR colon cancer cell lines; cisplatin was used as a positive control substance. The two dibutyltin(IV) cyanoximates showed cytotoxicity similar and greater to that of cisplatin. † Dedicated to Prof. R. D. Lampeka, Kiev State University, on the occasion of his 50th anniversary.
Cytotoxic Activity of Gd(III)- and Dy(III)-Complexes
Archiv der Pharmazie, 2007
The complexes of gadolinium(III) and dysprosium(III) were synthesized by reaction of the respective inorganic salts with 3,5-pyrazoledicarboxylic acid in amounts equal to metal to ligand molar ratio of 1 : 2. The structures of the final complexes were determined by means of spectral and elemental analyses. To help further the binding mode elucidation in the new Gd(III)-and Dy(III)-complexes of H 3 pdc, detailed vibrational analysis was performed on the basis of comparison of experimental vibrational spectra of the ligand and its Ln(III)-complexes using data theoretically predicted by us earlier, as well as data from the literature about related compounds. Significant differences in the IR and Raman spectra of the complexes were observed as compared to the spectra of the ligand. The ligand and the complexes were tested for their cytotoxic activities on the chronic myeloid leukemia-derived K-562, overexpressing the BCR-ABL fusion protein and the non-Hodgkin lymphoma-derived DOHH-2, characterized by a re-expression of the antiapoptotic protein bcl-2 cell lines. The results obtained indicate that the tested compounds exerted a considerable cytotoxic activity upon the evaluated cell lines in a concentrationdependent manner, which enabled the construction of dose-response curves and the calculation of the corresponding IC 50 values. The inorganic salts exerted a very weak cytotoxic effect on these cells. This is in contrast to the lanthanide complexes, which exhibited potent cytotoxic activity, even more than the activity of cisplatin towards K-562 and DOHH-2 cell lines.
Bulletin of Environmental Contamination and Toxicology, 1995
Organoehlorine compounds are widely employed and exist as residues in the environment. Some of the r are carcinogenic while others are not, even though they exhibit positive responses in short-term mutagenic assays. The main structural features affecting the carcinogenicity of organochlorine compounds are still unknown. Up to now, there is no effective way to predict whether or not organochlorine compounds are carcinogenic. ha this report, the genotoxicity of 41 organochlorine compounds are studied using discriminant analysis. We examined the experimental results of the Salmonella assay (Ames Test), and the cercinogenicity of these compounds to the mouse. Discdminant functions relating to the genotoxicity of organochlorine compounds were established based on molecular descriptors. MATERIALS AND METHODS The 41 compounds studied (Table 1), include chlorinated hydrocarbons, chlorinated aromatics and some pesticides, etc., which are extensively used. None ofthe 41 compounds contain amino or nitro groups. The mutagenicity and carcinogenicity data were taken from the U.S. National Toxicology Program (Ashby et al., 1991). Three kinds of genetoxieity indices were examined, the first involving the Salmonella assay (SA), the second, mouse liver carcinogenicity (CL), and the third, whole mouse carcinogenicity (CW) (tumors at all tissue sites). The three genotoxicity indices involving the 41 coml~unds are given in Table l. The compounds with positive effects were
Alternatives to Laboratory Animals, 2001
A new, mechanistically based, in vitro strategy involving Balb/c 3T3 clone A31-1-1 mouse embryo fibroblasts has been proposed for the determination of the carcinogenic potential of inorganic chemicals, in order to establish priority of metal compounds to be tested and, whenever possible, to compare the in vitro results with the corresponding in vivo data. As a first step in this research, this study reports on the cytotoxic effects of 58 metal compounds in the Balb/3T3 cell line. After harmonisation and standardisation of the Balb/3T3 protocol, cells were exposed for 72 hours to a fixed dose (100µM) of 58 individual compounds. The cytotoxicity induced by some metal compounds was found to be related to their chemical form (for example, Cr(NO 3) 3 and Na 2 CrO 4), suggesting that the Balb/3T3 cell line is a valuable cellular model in relation to this aspect of metal speciation. The results of the systematic study on the metalinduced cytotoxic effects in the Balb/3T3 cell line could be arbitrarily classified into three groups according to the degree of cytotoxicity. Group I includes 26 species that induced no observable effect or only a slight cytotoxic effect; Group II includes 13 metal compounds that exhibited an obvious degree of cytotoxicity; and Group III includes 19 metal species that displayed a strong cytotoxic response. Metal compounds of Groups II and III are considered to be of the highest priority for setting of dose-effect relationships for a subsequent in vitro study on metal-induced concurrent cytotoxicity and morphological transformation in the Balb/3T3 cell line.
The genotoxic evaluation (in vitro analysis) of a series of eight inorganic tin(II) and tin(IV) compounds [tin(II) acetate, tin(II) chloride, tin(II) ethylhexanoate, tin(II) oxalate, tin(II) oxide, tin(IV) acetate, tin(IV) chloride and tin(IV) oxide], for the detection of micronuclei in human blood lymphocytes, was performed in the absence of metabolic activation by the cytokinesisblock micronucleus assay. Human lymphocytes were treated for over one cell cycle (31 hours), with concentrations ranging from 1 to 75 mM (1, 5, 10, 20, 50 and 75 mM), of tin(II) and tin(IV) salts dissolved in dimethyl sulfoxide. The above-listed concentrations cover the values that have been detected in humans with no occupational exposure to tin compounds. The experimental results show the absence of genotoxicity for all inorganic compounds tested in the specific concentrations and experimental conditions. Cytotoxic effects of tin(II) and tin(IV) compounds were evaluated by the determination of cytokinesis block proliferation index and cytotoxicity percentage. Our observations on the cytotoxicity pattern of the tested tin(II) and tin(IV) compounds indicate that they are cytotoxic in several tested concentrations to human lymphocytes treated in vitro. The observed differences in cytotoxicity of each tested compound might reflect differences in their chemical structure.
Six coordination compounds: mode of cytotoxic action and biological evaluation
Journal of the Turkish Chemical Society, Section A: Chemistry, 2016
This study describes the biological and anticancer properties of coordination compounds given in the text. FT-IR spectra, magnetic properties, thermal analyses and crystal structures of six cyanido-complexes derivatives with [M II (CN)4] 2-(M II = Ni and Pd) and [Co(CN)6] 3anions and N,N-bishydeten (N,N-bis(2-hydroxyethyl)ethylenediamine) as a capping ligand have been reported previously. Here, we have investigated the pharmacological properties of these complexes denoted as [Ni(N-bishydeten)Ni(CN)4] (C1), [Zn2(N-bishydeten)2Ni(CN)4] (C2), [Ni(N-bishydeten)Pd(CN)4] (C3), [Cd(N-bishydeten)2][Pd(CN)4] (C4), [Ni2(Nbishydeten)2Co(CN)6].3H2O (C5) and K[Cd(N-bishydeten)Co(CN)6]. 3 2 ൗ H2O (C6), tested for their anti-proliferative activity against human cervical cancer (HeLa), human colon cancer (HT29), rat glioma (C6) and African green monkey kidney (Vero) cell lines. The DNA/BSA binding affinities of these compounds were also elucidated by spectroscopic titrations, displacement experiments, and electrophoresis measurements. Studies on cancerous cells revealed that C1, C2, C4 and C6 have exhibited the significant antitumor activity and inhibited tumor progression during testing cell lines and showed high solubility in the solvent. The results of absorbance and emission spectra data have revealed that the complexes interact with the DNA via groove binding mode of interaction. Overall, these compounds have been found to demonstrate effective antiproliferative activity against the cancer cell lines, indicating that they are a potent candidate for preclinical or clinical studies.