Cationic Pd(II)/Pt(II) 5,5-diethylbarbiturate complexes with bis(2-pyridylmethyl)amine and terpyridine: Synthesis, structures,DNA/BSA interactions, intracellular distribution, cytotoxic activity and induction of apoptosis

İçsel, Ceyda; Yılmaz, Veysel T.; Kaya, Yunus; Durmuş, Selvi; Sarimahmut, Mehmet; Büyükgüngör, Orhan; Ulukaya, Engin

doi:10.1016/j.jinorgbio.2015.08.026

Cited by 45 publications

(6 citation statements)

References 64 publications

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“…Moreover, ortho-substituted benzyl-rings on ligands exhibited better cytotoxic properties than their meta-/ para-substituted analogues [ 21 ]. A high activity of Pd compounds can result from increased DNA binding activity, but can also be related to different modes of action that may involve protein binding, endoplasmatic stress induction, or mitochondrial targeting [ 34 , 35 , 36 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Nickel(II), Palladium(II), and Platinum(II) Complexes with O,S Bidendate Cinnamic Acid Ester Derivatives: An In Vitro Cytotoxic Comparison to Ruthenium(II) and Osmium(II) Analogues

Hildebrandt

Häfner

Görls

et al. 2022

IJMS

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(1) Background: Since the discovery of cisplatin’s cytotoxic properties, platinum(II) compounds have attracted much interest in the field of anticancer drug development. Over the last few years, classical structure–activity relationships (SAR) have been broken by some promising new compounds based on platinum or other metals. We focus on the synthesis and characterization of 17 different complexes with β-hydroxydithiocinnamic acid esters as O,S bidendate ligands for nickel(II), palladium(II), and platinum(II) complexes. (2) Methods: The bidendate compounds were synthesized and characterized using classical methods including NMR spectroscopy, MS spectrometry, elemental analysis, and X-ray crystallography, and their cytotoxic potential was assessed using in vitro cell culture assays. Data were compared with other recently reported platinum(II), ruthenium(II), and osmium(II) complexes based on the same main ligand system. (3) Results: SAR analyses regarding the metal ion (M), and the alkyl-chain position (P) and length (L), revealed the following order of the effect strength for in vitro activity: M > P > L. The highest activities have Pd complexes and ortho-substituted compounds. Specific palladium(II) complexes show lower IC50 values compared to cisplatin, are able to elude cisplatin resistance mechanisms, and show a higher cancer cell specificity. (4) Conclusion: A promising new palladium(II) candidate (Pd3) should be evaluated in further studies using in vivo model systems, and the identified SARs may help to target platinum-resistant tumors.

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Section: Introductionmentioning

confidence: 99%

Novel Nickel(II), Palladium(II), and Platinum(II) Complexes with O,S Bidendate Cinnamic Acid Ester Derivatives: An In Vitro Cytotoxic Comparison to Ruthenium(II) and Osmium(II) Analogues

Hildebrandt

Häfner

Görls

et al. 2022

IJMS

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“…These values are in the same range as those found in other related Pd(II) and Pt(II) coordination compounds docked with DNA. 75,76 This energy is a combination of three primary factors, among which the van der Waals + H-bond + desolvation term plays the most important role, with energies of −9.90 and −9.31 kcal/mol for C1 and C2, respectively. The energetic difference in this term obtained for these two complexes reflects the presence of an intermolecular hydrogen bond between the carboxylate group of 1 and the amino group of DG3B (2.7 Å, C1 in Figure 11).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Ru(II) and Pt(II) Complexes Bearing Carboxyl Groups as Potential Anticancer Targeted Drugs

et al. 2017

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The synthesis and characterization of Pt(II) (1 and 2) and Ru(II) arene (3 and 4) or polypyridine (5 and 6) complexes is described. With the aim of having a functional group to form bioconjugates, one uncoordinated carboxyl group has been introduced in all complexes. Some of the complexes were selected for their potential in photodynamic therapy (PDT). The molecular structures of complexes 2 and 5, as well as that of the sodium salt of the 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine ligand (cptpy), were determined by X-ray diffraction. Different techniques were used to evaluate the binding capacity to model DNA molecules, and MTT cytotoxicity assays were performed against four cell lines. Compounds 3, 4, and 5 showed little tendency to bind to DNA and exhibited poor biological activity. Compound 2 behaves as bonded to DNA probably through a covalent interaction, although its cytotoxicity was very low. Compound 1 and possibly 6, both of which contain a cptpy ligand, were able to intercalate with DNA, but toxicity was not observed for 6. However, compound 1 was active in all cell lines tested. Clonogenic assays and apoptosis induction studies were also performed on the PC-3 line for 1. The photodynamic behavior for complexes 1, 5, and 6 indicated that their nuclease activity was enhanced after irradiation at λ = 447 nm. The cell viability was significantly reduced only in the case of 5. The different behavior in the absence or presence of light makes complex 5 a potential prodrug of interest in PDT. Molecular docking studies followed by molecular dynamics simulations for 1 and the counterpart without the carboxyl group confirmed the experimental data that pointed to an intercalation mechanism. The cytotoxicity of 1 and the potential of 5 in PDT make them good candidates for subsequent conjugation, through the carboxyl group, to "selected peptides" which could facilitate the selective vectorization of the complex toward receptors that are overexpressed in neoplastic cell lines.

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Section: Introductionmentioning

confidence: 99%

“…Noncovalent interaction, including electrostatic, groove binding, intercalation between the Pt(II) complex with DNA, has gained much more attention over the covalent interaction, which was laid out by cisplatin, carboplatin, and oxaliplatin. 23 There is another region which examined the affinity of drugs to serum albumin as it directly influences the drug concentration in the bloodstream. 24 In an attempt to assess their nature of interaction with DNA and bioavailability with respect to binding affinity with serum albumin, CT-DNA and bovine serum albumin (BSA) binding was performed 25 using absorption and fluorescence spectroscopy.…”

Section: ■ Introductionmentioning

confidence: 99%

Development of Anticancer Activity of the Pt(II) Complex with N-Heterocyclic Amine: Its In Vitro Pharmacokinetics with Thiol and Thio-Ethers, DNA and BSA Binding, and Cell Cycle Arrest

Pan

Mitra

Mukherjee

et al. 2021

ACS Appl. Bio Mater.

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A dichloro Pt(II) complex with N-heterocyclic amine cis-Pt(PIEAM)Cl2, C-1 (where PIEAM = 1-(2-aminoethyl)piperidine) was synthesized and hydrolyzed to the corresponding [Pt(PIEAM)(OH2)2]2+ C-2 to explore its bioactivity and cytotoxic property. Biorelevant sulfur-containing small tripeptide glutathione (GSH)- and amino acid dl-methionine (dl-meth)-substituted complexes [Pt(PIEAM)(GSH)] C-3 and [Pt(PIEAM)(dl-meth)]+2 C-4 were synthesized and characterized. In vitro pharmacokinetic reactions of complex C-2 → C-3 and C-4 with GSH and dl-meth, respectively, were studied under pseudo-first-order reaction conditions. The high and negative entropy of activation (ΔS ⧧) and low and positive enthalpy of activation (ΔH ⧧) values were deduced from the Eyring equation to propose an associative mechanism. To find out the biotransformation of complex C-1, C-2, and Pt(II)–S chelates C-3 and C-4 to Pt(II)-DNA adducts, DNA binding affinity of C-1–C-4 was examined by UV–visible spectroscopy, fluorescence quenching, and gel electrophoresis methods. BSA binding activity of these complexes was emphasized for their biological importance and the “drug reservoir” activity. Anticancer activity of these complexes on HEp 2 (laryngeal), MDA-MB-231 (breast), and A549 (lung) cancer cell lines was found to be remarkable as compared to the recognized anticancer drugs such as cisplatin, carboplatin, and oxaliplatin. Cell cycle arrest was also explored on HEp 2 cells of the complexes at a concentration corresponding to IC50 value and displayed significant cell death at the sub-G1 phase.

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Cationic Pd(II)/Pt(II) 5,5-diethylbarbiturate complexes with bis(2-pyridylmethyl)amine and terpyridine: Synthesis, structures,DNA/BSA interactions, intracellular distribution, cytotoxic activity and induction of apoptosis

Cited by 45 publications

References 64 publications

Novel Nickel(II), Palladium(II), and Platinum(II) Complexes with O,S Bidendate Cinnamic Acid Ester Derivatives: An In Vitro Cytotoxic Comparison to Ruthenium(II) and Osmium(II) Analogues

Novel Nickel(II), Palladium(II), and Platinum(II) Complexes with O,S Bidendate Cinnamic Acid Ester Derivatives: An In Vitro Cytotoxic Comparison to Ruthenium(II) and Osmium(II) Analogues

Synthesis and Biological Evaluation of Ru(II) and Pt(II) Complexes Bearing Carboxyl Groups as Potential Anticancer Targeted Drugs

Development of Anticancer Activity of the Pt(II) Complex with N-Heterocyclic Amine: Its In Vitro Pharmacokinetics with Thiol and Thio-Ethers, DNA and BSA Binding, and Cell Cycle Arrest

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