Osmium(III) analogues of KP1019: Electrochemical and chemical synthesis, spectroscopic characterization, x-ray crystallography, hydrolytic stability, and antiproliferative activity
Büchel, Gabriel E.
Jovanović, Katarina K.
Radulović, Siniša S.
Arion, Vladimir B.
KAUST DepartmentChemical Science Program
KAUST Catalysis Center (KCC)
Physical Science and Engineering (PSE) Division
Online Publication Date2014-10-07
Print Publication Date2014-10-20
Permanent link to this recordhttp://hdl.handle.net/10754/563803
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AbstractA one-electron reduction of osmium(IV) complexes trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole (0), 2H-indazole (0), 1H-imidazole (0), and 1H-benzimidazole (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), H2ind+ (H2ind), H2im+ (H2im), Ph4P+ (Ph4P), nBu4N+ (nBu4N), H2bzim+ (H2bzim), Ph4P+ (Ph4P), and nBu4N+ (nBu4N). All complexes were characterized by elemental analysis, 1H NMR spectroscopy, electrospray ionization mass spectrometry, UV-vis spectroscopy, cyclic voltammetry, while H2pz, H2ind, and nBu4, in addition, by X-ray diffraction. The reduced species - and - 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 and H2bzim exhibited significant antiproliferative activity in vitro when compared to H2pz and H2im. (Chemical Equation Presented).
SponsorsWe 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.
PublisherAmerican Chemical Society (ACS)
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Kuhn, P.-S., Büchel, G. E., Jovanović, K. K., Filipović, L., Radulović, S., Rapta, P., & Arion, V. B. (2015). CCDC 1049111: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/cc146p9b. DOI: 10.5517/cc146p9b HANDLE: 10754/624407
Kuhn, P.-S., Büchel, G. E., Jovanović, K. K., Filipović, L., Radulović, S., Rapta, P., & Arion, V. B. (2015). CCDC 1049112: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/cc146pbc. DOI: 10.5517/cc146pbc HANDLE: 10754/624408
Kuhn, P.-S., Büchel, G. E., Jovanović, K. K., Filipović, L., Radulović, S., Rapta, P., & Arion, V. B. (2015). CCDC 1049113: Experimental Crystal Structure Determination [Data set]. Cambridge Crystallographic Data Centre. https://doi.org/10.5517/cc146pcd. DOI: 10.5517/cc146pcd HANDLE: 10754/624409