Synthesis of platinum(II) complexes of isatin thiosemicarbazones derivatives: In vitro anti-cancer and deoxyribose nucleic acid binding activities (original) (raw)
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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.
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.
Journal of Inorganic Biochemistry, 2019
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Inorganic Chemistry, 1996
To obtain insight into the structure-activity relationships of new antitumor active platinum compounds the X-ray structure of the antitumor active Pt compound [Pt(bmic)Cl 2 ] (bmic ) bis-(N-methylimidazol-2-yl)carbinol) (1) and its interaction with short DNA fragments has been investigated using NMR spectroscopy. For comparison also the structurally related compound [Pt(bmi)Cl 2 ] (bmi ) N 1 ,N 1′ -dimethyl-2,2′-biimidazole) (2), which is not antitumor active, has been studied. The structure of the compound [Pt(bmic)Cl 2 ] (1) was characterized by singlecrystal X-ray structure determination. Compound 1 crystallizes in the monoclinic space group P2 1 /n, with a ) 10.055(3) Å, b ) 11.802(3) Å, c ) 10.620(3) Å, ) 103.78(2)°, V ) 1224.0(6) Å 3 and Z ) 4. Convergence was reached at wR2 ) 0.1148 (all data) and R1 ) 0.0476 (I > 2 (I)) for 2433 independent reflections and 156 adjustable parameters. The platinum atom is coordinated by two nitrogen and two chlorine atoms, resulting in a square planar PtN 2 Cl 2 coordination sphere. The two best least-squares planes through the two imidazole rings of the bmic ligand show a dihedral angle of 30.6°. The in Vitro and in ViVo antitumor activity of 1 is significant whereas for compound 2 no antitumor activity could be detected. In P388 mice leukemia an increase of lifespan of 56% was found for complex 1. The antitumor active Pt compound [Pt(bmic)Cl 2 ] binds to G bases in a similar fashion as cisplatin with a clear preference for N7. In reaction with d(GpG) two stereoisomers are formed, due to the unsymmetric bmic complex and the chiral d(GpG) molecule. Stereoisomer A, i.e. the isomer with the OH group of the bmic and the O6 of the G bases oriented on the same side of the Pt-N 4 plane, is preferentially formed. Modeling studies suggest that this preference is due to the presence of H bonds from the OH of the bmic moiety toward the O6 of the G bases. The presence of many conformers, present in solution, could also be due to these H bonds. For the inactive complex [Pt(bmi)Cl 2 ] only one GG-N7,N7 chelate is observed. Differences in reactivity toward G bases were also detected for the two platinum complexes. The inactive bmi complex proves to be the most reactive one, whereas the antitumor active bmic compound is less reactive. Thus both structural and kinetic properties may explain the different biological properties of these new platinum compounds.
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.
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...
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.