Examination of the effects of oxidation and ring closure on the cytotoxicities of the platinum complexes of N-(2-hydroxyethyl)ethane-1,2-diamine and ethane-1,2-diamine-N,N'-diacetic acid.
The crystal structures, electrochemical properties and cytotoxicities of platinum(II) and platinum(IV) complexes of the multidentate ligands N-(2-hydroxyethyl)ethane-1,2-diamine (NNOH) and ethane-1,2-diamine-N,N'-diacetic acid (H(2)enda) are reported. In the platinum(II) state the NNOH and H(2)enda ligands act as bidentate ligands, coordinating through the two amine groups with the hydroxyethyl and carboxylate groups remaining uncoordinated. Oxidation with hydrogen peroxide followed by refluxing yields the ring closed Pt(IV) complexes in which the NNOH and H(2)enda ligands are deprotonated and coordinate via the two amine groups and either the deprotonated alcohol group in the case of NNO or both carboxylato groups in the case of enda. The platinum(IV) complex of NNO is 2- to 5-fold more active against a panel of cisplatin sensitive and resistant human tumour cell lines than is the platinum(II) complex, whereas in the case of enda, the reverse is true. Ring closure to occupy both axial sites apparently leads to deactivation of platinum(IV) complexes, but a single closure does not necessarily do so.
Davies
Murray S
MS
Centre for Heavy Metals Research, School of Chemistry, University of Sydney, Sydney NSW 2006, Australia.
Wong
Pong Nai
PN
Battle
Andrew R
AR
Haddad
Gabi
G
McKeage
Mark J
MJ
Hambley
Trevor W
TW
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D018360:Crystallography, X-Ray; D003959:Diamines / Q000737:chemistry* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004563:Electrochemistry; D006801:Humans; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003959:Diamines; D009944:Organoplatinum Compounds; C466538:platinum(II) N-(2-hydroxyethyl)ethane-1,2-diamine; C466558:platinum(II) ethane-1,2-diamine-N,N'-diacetic acid