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In vitro pharmacological study of monomeric platinum(III) hematoporphyrin IX complexes

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Summary

Three stable mononuclear hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp) complexes of PtIII, namely cis-[ PtIII(NH3)2(Hp−3H)(H2O)2].H2O 1, [PtIII(Hp−3H)(H2O)2].H2O 2 and [PtIII((O,O)Hp−2H)Cl(H2O)3] 3 with distorted octahedral structure and (dz2)1 ground state have been tested in vitro for antineoplastic activity in a panel of tumor cell lines. The novel platinum(III) complexes showed cytotoxic activity in a concentration-dependent manner with IC50 values comparable to those of referent cytotoxic agent cisplatin together with lower cytotoxicity against renal cells. Further detailed evaluation of the active analogue 2 and the less active complex 3 showed that their potency greatly correlates with the ability to induce apoptosis and to bind DNA. Despite the structural dissimilarities between complex 2 and cisplatin, their DNA-adducts were equally effectively recognized and repaired by the nucleotide excision repair system. Complex 2 showed quite superior ability to accumulate in K-562 cells relative to cisplatin.

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Acknowledgements

This work has been financially supported by National Science Fund (Project-WU-06/05)- Bulgarian Ministry of Education and Sciences.

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Authors and Affiliations

  1. Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University, Sofia, 2 Dunav Str., 1000, Sofia, Bulgaria

    Georgi Momekov & Margarita Karaivanova

  2. Laboratory of Chromatin Structure and Functions, Institute of Molecular Biology, Bulgarian Academy of Sciences, G. Bonchev Str. Bl.21, 1113, Sofia, Bulgaria

    Iva Ugrinova & Evdokia Pasheva

  3. Department of Analytical Chemistry, Faculty of Chemistry, University of Sofia, 1 J. Bourchier Str., 1164, Sofia, Bulgaria

    Galina Gencheva, Daniela Tsekova, Sonia Arpadjan & Panayot R. Bontchev

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  1. Georgi Momekov
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  2. Margarita Karaivanova
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Correspondence to Georgi Momekov.

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Momekov, G., Karaivanova, M., Ugrinova, I. et al. In vitro pharmacological study of monomeric platinum(III) hematoporphyrin IX complexes. Invest New Drugs 29, 742–751 (2011). https://doi.org/10.1007/s10637-010-9412-8

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  • DOI: https://doi.org/10.1007/s10637-010-9412-8

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