Tetrakis(thione)platinum(II) complexes: synthesis, spectroscopic characterization, crystal structures, and in vitro cytotoxicity (original) (raw)
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Anticancer research
Platinum (II) complexes are accredited with biological activities. New complexes with thiepane dioxide diamine as ligands, characterized by defined stereochemical features, a flexible 7-membered thiepane moiety and by C2 symmetry, were prepared. The complexes, related to the diamino cyclohexane family of platinum complexes, were soluble in dimethyl sulfoxide with the solvent substituting one chloride ion. These positively-charged complexes were tested against a human carcinoma cell line A431 and its cisplatin-resistant counterpart A431/Pt and were found to show: i) capability in bypassing cisplatin-resistance; ii) cytotoxicity comparable to that of oxaliplatin; iii) lower activity than cisplatin. In both cells lines, [PtCl(DACH)(DMSO)]+ was more cytotoxic than oxaliplatin. The best activity was shown by the platinum complexes with ligands which presented C2 symmetry.
Anticancer activity assessment of two novel binuclear platinum (II) complexes
In the current study, two binuclear Pt (II) complexes, containing cis, cis-[Me 2 Pt (μ-NN) (μ-dppm) PtMe 2 ] (1), and cis,cis-[Me 2 Pt(μ-NN)(μ dppm) Pt((CH 2) 4)] (2) in which NN = phthalazine and dppm = bis (diphenylphosphino) methane were evaluated for their anticancer activities and DNA/purine nucleotide binding properties. These Pt (II) complexes, with the non-classical structures, demonstrated a significant anticancer activity against Jurkat and MCF-7 cancer cell lines. The results of ethidium bromide/acridine orange staining and Caspase-III activity suggest that these complexes were capable to stimulate an apoptotic mechanism of cell death in the cancer cells. Using different biophysical techniques and docking simulation analysis, we indicated that these complexes were also capable to interact efficiently with DNA via a non-intercalative mechanism. According to our results, substitution of cyclopentane (in complex 2) with two methyl groups (in complex 1) results in significant improvement of the complex ability to interact with DNA and subsequently to induce the anticancer activity. Overall, these binuclear Pt (II) complexes are promising group of the non-classical potential anticancer agents which can be considered as molecular templates in designing of highly efficient platinum an-ticancer drugs.
Bioinorganic Chemistry and Applications, 2003
Acylthiourea ligands, N,N-diphenyI-N'-benzoylthiourea (HL and N,N-diphenyI-N'-(p-nitrobenzoyl) thiourea (HL) were prepared in high yields (HL: 90%, HL2: 82%), by converting benzoyl chloride or pnitrobenzoyl chloride into the corresponding benzoyl isothiocyanate followed by reacting with diphenylamine. The cis-[PtL2] complexes have been synthesized by reaction of the ligands HL or HL with KzPtCI4 in a Pt:HL (1:2) molar ratio, in the presence of sodium acetate. The ligands and their cis-[PtL2] complexes have been characterized by elemental analysis, IR, FAB(+)-MS,H-NMR,3C-NMR and 95pt-NMR. The molecular structure of cis-bis(N,N-diphenyI-N'-benzoylthioureato) platinum(II) shows a squareplanar geometry with two deprotonated ligands (L) coordinated to Pt(II) through the oxygen and sulfur atoms in a cis arrangement. The antitumor activity of the ligands and their cis-[PtL2] complexes was evaluated on mouse mammary adenocarcinoma TA3. The ICs0.values of culture growth for ligands HL and HL were 23.1 and 34.9 tM, respectively, whereas for the cis-[PtL2] complexes they were in the range of 2.6-2.8 laM, which indicates that the platinum(|I) complexes are about 10-fold more cytotoxic than the free ligands and a participation of nitro group in the complex activity is slightly relevant.
RSC Advances, 2016
Heteroleptic platinum(II) dithiocarbamates, of general formula [Pt(DTC)LCl], where DTC = 4-(4-methoxyphenyl)piperazine-1-carbodithioate (1 and 2) and 4-(furan-2-carbonyl)piperazine-1-carbodithioate (3) and L = tri(4-flourophenylphosphine) (1 and 3) and tri(4-chlorophenylphosphine) (2) have been synthesized and characterized by different analytical techniques. These complexes are square planar with picoplatin or phenanthriplatin type steric hindrance from aromatic C–H groups of the phosphine ligand as shown by single-crystal analysis. In 1, the Pt square plane is hindered by two axially oriented hydrogens, whereas by only one in 2 and 3. DNA-binding studies by UV/visible spectroscopy revealed a stronger electrostatic interaction of 1 compared to 2 and 3, and the results are further supported by viscometry and cyclic voltammetric measurements. Their in vitro anticancer activity against five different cancer cell lines using a MTT assay revealed high potency of the complexes. The higher activity of 1 than both 2 and 3 is consistent with DNA binding strength and we speculate that it may be due to the relatively inert nature of platinum towards off-target biomolecules ensured by the hindrance caused by the two axially oriented hydroge
Cytotoxic Effect of Two Novel Platinum (II) Complexes on Breast Cancer: An in Vitro Study
Asian Pacific journal of cancer biology, 2018
Background: With 1.36 million new cases in worldwide each year, breast cancer (BC) is the most common malignancy in the female. Among numerous chemotherapy drugs which are widely used for cancer therapy, platinum compounds are the most persuasive ones although challenges remain with the clinical use of them due to their side effects as well as intrinsic and acquired resistance. In the attempt to combat drug resistance, reduce cytotoxic side effects or find the drug for particular forms of cancer, over the years, thousands of other platinum (Pt) compounds i.e. carboplatin and oxaliplatin have been developed. Material and Methods: In this regard, we previously described the synthesis of some new platinum (II) derivatives with potential anti-cancer activities against BC. Here, we chose two of the best platinum(II) compounds, 3b and 2a, to further evaluate their cytotoxic activities against human BC cell lines, SKBR3, MCF-7, MDA-MB-231, and MBA-MB-468, with different molecular subtypes using a colorimetric MTT cytotoxic assay. Their cytotoxic activities were compared to cis-platin as a positive control. Results: Our result showed that both compounds had better cytotoxic effect against BC cell lines than cis-platin in particular in the case of triple-negative subtype. Conclusion: These results suggest these compounds as potentially valuable agents for the treatment of breast cancer patients.
2020
Eight platinum(II) complexes with anticancer potential have been synthesised and characterised. These complexes are of the type [ , where I L is either dipyrido[3,2-f:2',3'-h]quinoxaline (dpq) or 2,3-dimethyl-dpq (23Me 2 dpq) and A L is one of the R,R or S,S isomers of either 1,2-diaminocyclohexane (SS-dach or RR-dach) or 1,2-diaminocyclopentane (SS-dacp or RR-dacp). The CT-DNA binding of these complexes and a series of other complexes were assessed using fluorescent intercalator displacement assays, resulting in unexpected trends in DNA binding affinity. The cytotoxicity of the eight synthesised compounds was determined in the L1210 cell line; the most cytotoxic of these were [Pt(dpq)(SS-dach)]Cl 2 and [Pt(dpq)(RR-dach)]Cl 2 , with IC 50 values of 0.19 and 0.80 μM, respectively. The X-ray crystal structure of the complex [Pt(dpq)(SS-dach)](ClO 4 ) 2 ·1.75H 2 O is also reported.