Synthesis, structure and in vitro cytotoxic studies of novel paramagnetic palladium(III) complexes with hematoporphyrin IX

Tsekova, Daniela; Gorolomova, Paulina; Gochev, G.; Skumryev, V.; Momekov, Georgi; Momekova, Denitsa; Gencheva, G.

doi:10.1016/j.jinorgbio.2013.03.012

Cited by 9 publications

(24 citation statements)

References 47 publications

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“…According to Palanimuthu et al (2013), complexes formed by bis-(thiosemicarbazone) with copper substantially inhibit DNA synthesis and lead to the induction of apoptosis in tumor cells HCT116 (colorectal cancer). Tsekova et al (2013) found that coordination compounds of Pd(II) with hematoporphyrin led to growth inhibition of human tumor cell lines. They observed that cell growth inhibitory effects were related to the induction of programmed cell death through apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic effect of inositol hexaphosphate and its Ni(II) complex on human acute leukemia Jurkat T cells

Lima

Kanunfre

Andrade

et al. 2015

Toxicology in Vitro

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Inositol hexaphosphate (InsP6) is present in cereals, legumes, nuts and seed oils and is biologically active against some tumor and cancer cells. Herein, this study aimed at evaluating the cellular toxicity, antiproliferative activity and effects on cell cycle progression of free InsP6 and InsP6-Ni(II) of leukemic T (Jurkat) and normal human cells. Treatments with InsP6 at concentrations between 1.0 and 4.0mM significantly decreased the viability of Jurkat cells, but showed no cytotoxic effect on normal human lymphocytes. Treatment with InsP6-Ni(II) complex at concentrations between 0.05 and 0.30 mM showed an anti-proliferative dose and a time-dependent effect, with significantly reduced cell viability of Jurkat cells but showed no cytotoxic effect on normal human lymphocytes as compared to the control. Ni(II) free ion was toxic to normal cells while InsP6-Ni(II) had no cytotoxic effect. The InsP6-Ni(II) complex potentiated (up to 10×) the antiproliferative effect of free InsP6 on Jurkat cells. The cytometric flow assay showed that InsP6 led to an accumulation of cells in the G0/G1 phase of the cell cycle, accompanied by a decrease in the number of cells in S and G2/M phases, whereas InsP6-Ni(II) has led to an accumulation of cells in the S and G2/M phases. Our findings showed that InsP6-Ni(II) potentiates cytotoxic effects of InsP6 on Jurkat cells and may be a potential adjuvant in the treatment of cancer.

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Section: Discussionmentioning

confidence: 99%

Cytotoxic effect of inositol hexaphosphate and its Ni(II) complex on human acute leukemia Jurkat T cells

Lima

Kanunfre

Andrade

et al. 2015

Toxicology in Vitro

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“…Recently, a series of hematoporphyrin IX (7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid, Hp) complexes [32,33,34,35,36,37,38,39] of platinum, palladium, and gold (Scheme 1) have been tested as tumor growth inhibitors. Hematoporphyrin IX and its derivatives are well known for their widespread application in the photodynamic therapy and diagnosis [40].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, three Pt III (d 7 ) [32,33], two Pd III (d 7 ) [34], and one Au II (d 9 ) [35,36] complexes of Hp were obtained and characterized. The metal ions in the complexes have distorted octahedral coordination.…”

Section: Introductionmentioning

confidence: 99%

“…Because of the metals’ electronic configuration, the complexes manifest paramagnetic behavior. Further they show comparatively high cytotoxicity in in vitro tests against a panel of human cell lines [32,33,34,36]. Great efforts have been made in order to understand the effect of the ligand coordination to the antitumor behavior of the complexes.…”

Section: Introductionmentioning

confidence: 99%

“…The ligand Hp has a polydentate nature. Three different modes of coordination have been established [37] studying its interaction with metal ions representatives of first [38,39], second [34], and third transition series [32,33,35,36]. Coordination via the four pyrrole N-atoms in the porphyrin framework and forming of metalloporphyrin-type complexes is the most widespread mode of binding, typical of all metal ions under investigation.…”

Section: Introductionmentioning

confidence: 99%

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Cellular Pharmacology of Palladinum(III) Hematoporphyrin IX Complexes: Solution Stability, Antineoplastic and Apoptogenic Activity, DNA Binding, and Processing of DNA-Adducts

Momekov

Ugrinova

Pasheva

et al. 2018

IJMS

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Two paramagnetic PdIII complexes of hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp), namely a dinuclear one [PdIII2(Hp-3H)Cl3(H2O)5]·2PdCl2, Pd1 and a mononuclear metalloporphyrin type [PdIII(Hp-2H)Cl(H2O)]·H2O, Pd2 have been synthesized reproducibly and isolated as neutral compounds at different reaction conditions. Their structure and solution stability have been assayed by UV/Vis and EPR spectroscopy. The compounds researched have shown in vitro cell growth inhibitory effects at micromolar concentration against a panel of human tumor cell lines. A DNA fragmentation test in the HL-60 cell line has indicated that Pd1 causes comparable proapoptotic effects with regard to cisplatin but at substantially higher concentrations. Pd1 and cisplatin form intra-strand guanine bis-adducts as the palladium complex is less capable of forming DNA adducts. This demonstrates its cisplatin-dissimilar pharmacological profile. The test for efficient removal of DNA-adducts by the NER synthesis after modification of pBS plasmids with either cisplatin or Pd1 has manifested that the lesions induced by cisplatin are far better recognized and repaired compared those of Pd1. The study on the recognition and binding of the HMGB-1 protein to cisplatin or Pd1 modified DNA probes have shown that HMG proteins are less involved in the palladium agent cytotoxicity.

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Mechanistic details on Pd(II)/5,10,15,20-tetrakis(1-methyl-4-pyridyl)porphyrin complex formation and reactivity in the presence of DNA

et al. 2017

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Kinetics of coordination of Pd(II) by the macrocyclic porphyrin 5,10,15,20-tetrakis(1-methyl-4-pyridyl)porphyrin (H2P4+) is investigated and confirms quantitative formation of a planar PdP4+complex at room temperature (formation rate 0.19 M-1 s-1 at 25 °C, 0.2 M NaCl, pH 3). Then, the binding ability to DNA of the pre-formed PdP4+complex is analysed. To achieve this aim, spectrophotometry, spectrofluorometry and viscometry are used. Thermodynamic parameters for binding, obtained by the temperature dependence of the equilibrium constants, are deltaH = -71 kJ mol-1 and deltaS = -134 J mol-1 K-1. These values, being both highly negative, agree with full PdP4+intercalation into DNA. Moreover, kinetics of the binding reaction is analysed by the T-jump technique (reaction times in the 1-5 ms range). Experiments on the porphyrin ligand retention on negative SDS and positive DTAC micellar surfaces are also done. Taken altogether, these data provide mechanistic details on complex formation and on DNA binding and relevant energies and driving forces. It is found that interaction between PdP4+and base pairs is very strong (KabsDNA = 8.0E5 M-1 at 25 °C, 1.0 M NaCl), not only owing to the high positive charge borne by the complex, but also to the contribution of high hydrophobicity of the porphyrin ring. In the dye/DNA complex, PdP4+is buried into the helix, as confirmed also by fluorescence quenching tests. Both presence and type of metal ion play a major role, as lower affinity and lower induced helix conformation changes are found in the case of the H2P4+/DNA and CuP4+/DNA systems

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Synthesis, structure and in vitro cytotoxic studies of novel paramagnetic palladium(III) complexes with hematoporphyrin IX

Cited by 9 publications

References 47 publications

Cytotoxic effect of inositol hexaphosphate and its Ni(II) complex on human acute leukemia Jurkat T cells

Cytotoxic effect of inositol hexaphosphate and its Ni(II) complex on human acute leukemia Jurkat T cells

Cellular Pharmacology of Palladinum(III) Hematoporphyrin IX Complexes: Solution Stability, Antineoplastic and Apoptogenic Activity, DNA Binding, and Processing of DNA-Adducts

Mechanistic details on Pd(II)/5,10,15,20-tetrakis(1-methyl-4-pyridyl)porphyrin complex formation and reactivity in the presence of DNA

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