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American Chemical Society, Journal of Medicinal Chemistry, 9(50), p. 2185-2193, 2007

DOI: 10.1021/jm061081y

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Structure-Activity Relationships for NAMI-A-type Complexes (HL)[trans-RuCl4L(S-dmso)ruthenate(III)] (L = Imidazole, Indazole, 1,2,4-Triazole, 4-Amino-1,2,4-triazole, and 1-Methyl-1,2,4-triazole): Aquation, Redox Properties, Protein Binding, and Antiproliferative Activity

Journal article published in 2007 by Michael Groessl, Erwin Reisner, Christian G. Hartinger, Rene Eichinger, Olga Semenova, Andrei R. Timerbaev, Michael A. Jakupec ORCID, Vladimir B. Arion, Bernhard K. Keppler
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Imidazolium [trans-tetrachloro(1H-imidazole)(S-dimethylsulfoxide)ruthenate(III)] (NAMI-A) and indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) are the most promising ruthenium complexes for anticancer chemotherapy. In this study, the azole ligand of NAMI-A was systematically varied (from imidazole of NAMI-A to indazole, 1,2,4-triazole, 4-amino-1,2,4-triazole, and 1-methyl-1,2,4-triazole), and the resp. complexes were evaluated with regard to the rate of aquation and protein binding, redox potentials, and cytotoxicity by means of capillary zone electrophoresis, electrospray ionization mass spectrometry, cyclic voltammetry, and colorimetric microculture assays. Stability studies demonstrated low stability of the complexes at pH 7.4 and 37 DegC and a high reactivity toward proteins (binding rate consts. in the ranges of 0.02-0.34 and 0.01-0.26 min-1 for albumin and transferrin, resp.). The redox potentials (between 0.25 and 0.35 V) were found to be biol. accessible for activation of the complexes in the tumor, and the indazole-contg. compd. shows the highest antiproliferative activity in vitro. [on SciFinder (R)] ; CAN 147:22703 1-3 Pharmacology Institute of Inorganic Chemistry,University of Vienna,Vienna,Austria. Journal 938076-98-3P; 938077-00-0P Role: PAC (Pharmacological activity), PRP (Properties), RCT (Reactant), SPN (Synthetic preparation), THU (Therapeutic use), BIOL (Biological study), PREP (Preparation), USES (Uses), RACT (Reactant or reagent) (SAR of NAMI-A ruthenium complexes: aquation, redox properties, protein binding, and antitumor action); 201653-76-1; 783324-95-8; 783325-20-2 Role: PAC (Pharmacological activity), PRP (Properties), THU (Therapeutic use), BIOL (Biological study), USES (Uses) (SAR of NAMI-A ruthenium complexes: aquation, redox properties, protein binding, and antitumor action); 938077-02-2P; 938077-04-4P Role: PRP (Properties), SPN (Synthetic preparation), PREP (Preparation) (SAR of NAMI-A ruthenium complexes: aquation, redox properties, protein binding, and antitumor action); 584-13-4 (4H-1,2,4-Triazol-4-amine); 1100-88-5; 6086-21-1; 135908-81-5 Role: RCT (Reactant), RACT (Reactant or reagent) (SAR of NAMI-A ruthenium complexes: aquation, redox properties, protein binding, and antitumor action)