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Int. J. Mol. Sci. 2018, 19(8), 2451; https://doi.org/10.3390/ijms19082451

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

1
Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., BG1000 Sofia, Bulgaria
2
Laboratory of Chromatin Structure and Functions, Institute of Molecular Biology, Bulgarian Academy of Sciences, G. Bonchev Str. Bl.21, BG1113 Sofia, Bulgaria
3
Department of Analytical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University, 1 J. Bourchier Str., BG1164 Sofia, Bulgaria
*
Authors to whom correspondence should be addressed.
Received: 21 July 2018 / Revised: 11 August 2018 / Accepted: 12 August 2018 / Published: 19 August 2018
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Abstract

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. View Full-Text
Keywords: palladium(III) complexes; hematoporphyrin IX; antiproliferative activity; DNA binding and repair; HMGB-1 protein; apoptosis palladium(III) complexes; hematoporphyrin IX; antiproliferative activity; DNA binding and repair; HMGB-1 protein; apoptosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Momekov, G.; Ugrinova, I.; Pasheva, E.; Tsekova, D.; Gencheva, G. Cellular Pharmacology of Palladinum(III) Hematoporphyrin IX Complexes: Solution Stability, Antineoplastic and Apoptogenic Activity, DNA Binding, and Processing of DNA-Adducts. Int. J. Mol. Sci. 2018, 19, 2451.

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