Cytotoxicity of some platinum(IV) complexes with ethylenediamine-N,N'-di-3-propionato ligand
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The cytotoxicities of two platinum(IV) complexes of formula [PtX(2)(eddp)] - nH(2)O (eddp = ethylenediamine-N,N'-di-3-propionate, X = chloro [11 or bromo , n = I or 1.24) are reported. The complexes have been obtained by direct reaction of potassium hexahaloplatinate(IV) with H(2)eddp.2HCl followed by addition of a base (LiOH). The crystal and molecular structure has confirmed that the complex with bromo ligands, similarly to the complex with chloro ligands previously reported, has trans configuration of the halogens. In both the chloro and bromo complexes there appear to be intramolecular N-H... X interactions which account for a narrowing of the corresponding X-Pt-N angles below 90degrees. The trans isomer (configuration index OC-6-13, two nitrogens and two oxygens of eddp bound in the equatorial plane) is the only one obtained in the reaction of hexahaloplatinate(IV) with the eddp ligand while a similar reaction performed with ethylenediamine-N,N'-diacetate (edda) affords exclus...ively the symmetrical cis-isomer (configuration index OC-6-33, equatorial nitrogen and axial oxygen atoms of edda). The longer chain of the propionato groups (as compared to the acetato ones) is responsible for such a change in preferred configuration. NMR data have revealed a very large diastereotopic splitting of the propionato methylene protons a to the nitrogens (0.88 ppm). The trans disposition of the halogen ligands in the compounds with eddp leads to deactivation of platinum(IV) complexes in comparison to those with edda having cis disposition of the leaving chlorides (human ovarian cancer cell line A2780, IC(50) [muM] of 92.6 +/- 12 and 30.3 +/- 7.5 for  and , respectively). (C) 2004 Elsevier Inc. All rights reserved.
Кључне речи:platinum(IV) complexes / crystal structure / cytotoxicity / eddp ligand
Извор:Journal of Inorganic Biochemistry, 2004, 98, 8, 1378-1384
- Elsevier Science Inc, New York