Osmium(III) analogues of KP1019: Electrochemical and chemical synthesis, spectroscopic characterization, x-ray crystallography, hydrolytic stability, and antiproliferative activity

Paul-Steffen Kuhn, Gabriel E. Büchel, Katarina K. Jovanović, Lana Filipović, Siniša S. Radulović, Peter Rapta, Vladimir B. Arion

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22 Scopus citations

Abstract

A one-electron reduction of osmium(IV) complexes trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole ([1]0), 2H-indazole ([2]0), 1H-imidazole ([3]0), and 1H-benzimidazole ([4]0), afforded a series of eight new complexes as osmium analogues of KP1019, a lead anticancer drug in clinical trials, with the general formula (cation)[trans-OsIIICl4(Hazole)2], where cation = H2pz+ (H2pz[1]), H2ind+ (H2ind[2]), H2im+ (H2im[3]), Ph4P+ (Ph4P[3]), nBu4N+ (nBu4N[3]), H2bzim+ (H2bzim[4]), Ph4P+ (Ph4P[4]), and nBu4N+ (nBu4N[4]). All complexes were characterized by elemental analysis, 1H NMR spectroscopy, electrospray ionization mass spectrometry, UV-vis spectroscopy, cyclic voltammetry, while H2pz[1], H2ind[2], and nBu4[3], in addition, by X-ray diffraction. The reduced species [1]- and [4]- are stable in aqueous media in the absence of air oxygen and do not react with small biomolecules such as amino acids and the nucleotide 5′-dGMP. Cell culture experiments in five different human cancer cell lines (HeLa, A549, FemX, MDA-MB-453, and LS-174) and one noncancerous cell line (MRC-5) were performed, and the results were discussed and compared to those for KP1019 and cisplatin. Benzannulation in complexes with similar structure enhances antitumor activity by several orders of magnitude, implicating different mechanisms of action of the tested compounds. In particular, complexes H2ind[2] and H2bzim[4] exhibited significant antiproliferative activity in vitro when compared to H2pz[1] and H2im[3]. (Chemical Equation Presented).
Original languageEnglish (US)
Pages (from-to)11130-11139
Number of pages10
JournalInorganic Chemistry
Volume53
Issue number20
DOIs
StatePublished - Oct 7 2014

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We thank A. Dobrov for ESI mass spectra measurements, A. Roller for collection of the X-ray data, and M. Malarek for reading the manuscript and helpful discussion. We are thankful to the Ministry of Science and Technology of Serbia for financial support from Grant No. III41026. P.R. thanks the Science and Technology Assistance Agency (Contract No. SK-AT-0027-12) and Slovak Grant Agency VEGA (Grant No. 1/0307/14) for financial support.

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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