Pt(II) complexes of the antitumor agent 2-formylpyridine thiosemicarbazone (original) (raw)
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Journal of Chemistry
In a bid to come up with potential anticancer agents, a class of thiosemicarbazone ligands bearing substituted thiophene were synthesized followed by complexation with various Pd(II) and Pt(II) metal precursors. The ligands (E)-1-((thiophen-2-yl)methylene)thiosemicarbazide (L1), (E)-1-((4-bromothiophen-2-yl)methylene)thiosemicarbazide (L2), and (E)-1-((5-bromothiophen-2-yl)methylene)thiosemicarbazide (L3) were synthesized by condensation reactions and obtained in good yields. Complexation of L1 and L2 with Pd(cod)Cl2 gave C1 (C6H7Cl2N3PdS2) and C2 (C6H6BrCl2N3PdS2), respectively. Complexation of L1 with K2PtCl4 gave C3 (C6H7Cl2N3PtS2), while L3 with K2PtCl2[(PPh)3]2 gave C4 (C24H21BrClN3PPtS2). The structures and coordination for all compounds were established by FTIR, 1H-NMR, 13C-NMR, UV-Vis, elemental analysis, and single-crystal X-ray diffraction studies for ligand L1. Tuning of the spectral and anticancer activity of the compounds was investigated by changing the position of the...
Inorganica Chimica Acta, 2014
Six new platinum(II) complexes of a thiosemicarbazone Schiff base with isatin moiety [PtL1 to Pt(L6) 2 ] were synthesized by the reaction of platinum(II) with the following: (Z)-2-(2-oxoindolin-3-ylidene)-N-phenylhydrazinecarbothioamide [L1H], (Z)-2-(5-methyl-2oxoindolin-3-ylidene)-N-phenylhydrazinecarbothioamide [L2H], (Z)-2-(5-fluoro-2oxoindolin-3-ylidene)-N-phenylhydrazinecarbothioamide [L3H], (Z)-N-methyl-2-(5-nitro-2oxoindolin-3-ylidene)hydrazinecarbothioamide [L4H], (Z)-N-methyl-2-(5-methyl-2oxoindolin-3-ylidene)hydrazinecarbothioamide [L5H], and (Z)-N-ethyl-2-(5-methyl-2oxoindolin-3-ylidene)hydrazinecarbothioamide [L6H]. The structures of these complexes were characterized by elemental analysis, IR, UV-vis, 1 H NMR, and mass spectrometry analyses. The structure of Pt(L6) 2 was further characterized by single-crystal XRD. The interaction of these complexes with calf thymus (CT) DNA exhibited a high intrinsic binding constant (K b = 3.5 × 10 4 to 3.29 × 10 6 M-1), which reflected the intercalative activity of these complexes toward CT DNA. This result was also confirmed by viscosity data. Data obtained from the in vitro anti-proliferative study clearly established the anticancer potency of PtL1, PtL2, PtL3, PtL5, and Pt(L6) 2 against the human colorectal carcinoma cell line HCT 116.
Journal of Medicinal Chemistry, 1998
The reaction of p-isopropylbenzaldehyde thiosemicarbazone [p-is.TSCN], 1, with palladium-(II) acetate and potassium tetrachloroplatinate yielded two tetrameric orthopalladated isomers, [Pd(p-is.TSCN)] 4 (complexes 2 and 3), and the platinum analogue [Pt(p-is.TSCN)] 4 (complex 4), respectively. All of these complexes contain the thiosemicarbazone bonded as a terdentate ligand to the metallic atom, through the thiol sulfur, the azomethinic nitrogen and the ortho carbon of the p-isopropylphenyl ring to which the imine group is attached to as deduced from the study of the IR, NMR, and XRD spectra of complexes 2 and 4. Complexes 2 and 4 crystallize in the centrosymmetric monoclinic space group C2/c, with Z ) 8. Unit cell parameters for complex 2 are as follows: a ) 25.742 Å, b ) 19.560(4) Å, c ) 24.199(5) Å, ) 101.70(3) o . Unit cell parameters for complex 4 are as follows: a ) 25.8728(19) Å, b ) 19.5053(14) Å, c ) 24.0899(16) Å, ) 101.305 o . As can be deduced from the NMR study, the palladated isomers 2 and 3 interconvert in DMSO which may be a consequence of the existence in both complexes of a flexible eight-membered ring with alternating Pd-S atoms. The testing of the cytotoxic activity of these compounds against several human and murine cell lines sensitive and resistant to cisplatin (cis-DDP) suggests that compounds 2, 3, and 4 may be endowed with important anticancer properties since they elicit IC 50 values in the µM range as does the clinically used drug cis-DDP, and, moreover, they display cytotoxic activity in tumor lines resistant to cis-DDP. The analysis of the interaction of these novel tetrameric cyclometalated compounds with DNA suggests that they form DNA interhelical cross-links.
Inorganic Chemistry Communications, 2013
Reaction of 2,6-diacetylpyridine bis( 4 N-o-tolylthiosemicarbazone), H 2 L 1 , with K 2 PtCl 4 and further recrystallization in DMSO/MeOH of the [PtL 1 ] complex obtained, led to the isolation of the novel platinum complex, [PtL 2 ], which was structurally characterized by single crystal X-ray diffraction. The molecular structure shows that the ligand has undergone an unexpected chemical transformation viz. reduction of one of the terminal phenyl rings into cyclohexyl. The resulted asymmetrical ligand acts a dianionic tetradentate donor, coordinating to the platinum(II) center in a square planar geometry through the N pyridinic atom and the N iminic and the S atoms from one thiosemicarbazone arm, the fourth coordination position is occupied by the N hydrazinic atom of the other arm.
Journal of Inorganic Biochemistry, 2014
Preparation and characterization of 2,6-diacetylpyridine bis( 4 N-p-chlorophenylthiosemicarbazone) ligand, H 2 L, and its palladium(II) and platinum(II) complexes [PdL] and [PtL], is described. The molecular structure of the two new complexes has been determined by single crystal X-ray diffraction. The ligand acts as dianionic tetradentate donor coordinating to the metal center in a square planar geometry through the pyridine nitrogen atom and the azomethine nitrogen and thione sulfur atoms from one thiosemicarbazone arm, the fourth coordination position is occupied by the hydrazine nitrogen atom of the other arm. New free ligand and its metal complexes have been evaluated for antiproliferative activity in vitro against NCI-H460, T-47D, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H 2 L and [PtL] since they are capable of not only circumvent cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in breast cancer T-47D cells. The interaction of H 2 L with calf thymus DNA was also investigated and its binding constant (Kb) determined.
RSC Advances, 2023
Nine tridentate Schiff base ligands of the type (N^N^O) were synthesized from reactions of primary amines {2-picolylamine (Py), N-phenyl-1,2-diaminobenzene (PhN), and N-phenyl-1,2-diaminoethane(EtN)} and salicylaldehyde derivatives {3-ethoxy (OEt), 4-diethylamine (NEt 2) and 4-hydroxy (OH)}. Complexes with the general formula Pt(N^N^O)Cl were synthesized by reacting K 2 PtCl 4 with the ligands in DMSO/ ethanol mixtures. The ligands and their complexes were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. The DNA-binding behaviours of the platinum(II) complexes were investigated by two techniques, indicating good binding affinities and a two-stage binding process for seven complexes: intercalation followed by switching to a covalent binding mode over time. The other two complexes covalently bond to ct-DNA without intercalation. Theoretical calculations were used to shed light on the electronic and steric factors that lead to the difference in DNA-binding behavior. The reactions of some platinum complexes with guanine were investigated experimentally and theoretically. The binding of the complexes with bovine serum albumin (BSA) indicated a static interaction with higher binding affinities for the ethoxy-containing complexes. The half maximal inhibitory concentration (IC 50) values against MCF-7 and HepG2 cell lines suggest that platinum complexes with tridentate ligands of N-phenyl-o-phenylenediamine or pyridyl with 3-ethoxysalicylimine are good chemotherapeutic candidates. Pt-Py-OEt and Pt-PhN-OEt have IC 50 values against MCF-7 of 13.27 and 10.97 mM, respectively, compared to 18.36 mM for cisplatin, while they have IC 50 values against HepG2 of 6.99 and 10.15 mM, respectively, compared to 19.73 mM for cisplatin. The cell cycle interference behaviour with HepG2 of selected complexes is similar to that of cisplatin, suggesting apoptotic cell death. The current work highlights the impact of the tridentate ligand on the biological properties of platinum complexes.
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 2003
The reactions of Pd(II) and Pt(II) with 2-Acetyl Pyridine N(4)-Ethyl-Thiosemicarbazones, HAc4Et and 2-Acetyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl Thiosemicarbazone, HAc4PiPiz and 2-Formyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl Thiosemicarbazone, HFo4PiPiz afforded the complexes, [Pd(Ac4Et)], 1, [Pd(HAc4Et)2]Cl2, 2 and [Pd(Ac4Et)2], 3 [Pt(Ac4Et)], 4, [Pt(HAc4Et)2]Cl2, 5, [Pt(Ac4Et)2], 6 and [Pd(Fo4PipePiz)Cl], 7, [Pd(Fo4PipePiz)2], 8, [Pd(Ac4PipePiz)Cl], 9 and [Pd(Ac4PipePiz)2], 10. The crystal structure of the complex [Pt(Ac4Et)2], 6 has been solved. The platinum(II) atom is in a square planar environment surrounded by two cis nitrogen atoms and two cis sulfur atoms. The ligands are not equivalent, one being tridentate with (N,N,S) donation, the other being monodentate using only the sulfur atom to coordinate to the metal. The tridentate ligand shows a Z, E, Z configuration while the monodentate ligand shows an E, E, Z. Inter-molecular hydrogen bonds stabilize the structure, whi...
Anticancer activity and DNA-binding properties of novel cationic Pt(II) complexes
International Journal of Biological Macromolecules, 2014
In this study, three structurally related cationic Pt complexes, [Pt(ppy)(dppe)]CF 3 CO 2 : C 1 , [Pt(bhq)(dppe)]CF 3 CO 2 : C 2 , and [Pt(bhq)(dppf)]CF 3 CO 2 : C 3 , in which ppy = deprotonated 2phenylpyridine, bhq = deprotonated benzo[h]quinoline, dppe = bis(diphenylphosphino)ethane and dppf = 1,1-bis(diphenylphosphino)ferrocene, were used for the assessment of their anticancer activities against Jurkat and MCF-7 cancer cell lines. The Pt complexes (C 1-C 3) demonstrated significant level of anticancer properties, as measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Moreover, the changes in nuclear morphology with Acridine Orange (AO) staining reveal that these complexes are capable to induce apoptosis, and only C 1 stimulates activity of Caspase-3 in Jurkat cancer cells. To get a better insight into the nature of binding between these cationic Pt complexes and DNA, different spectroscopic techniques and gel electrophoresis were applied. On the basis of the results of UV/vis absorption spectroscopy, CD experiment and fluorescence quenching of ethidium bromide (EB)-DNA, the interaction between DNA and the Pt complexes is likely to occur through a mixed-binding mode. Overall, the present work suggests that a controlled modification could result in new potentially antitumor complexes which can survive the repair mechanism and induce facile apoptosis.