Antitumor Trans Platinum Adducts of GMP and AMP. Issue 4 (2000)

• Record Type: Journal Article
• Authors: Liu Liu, Yangzhong Yangzhong; Sivo Sivo, Maria F. Maria F.; Natile Natile, Giovanni Giovanni; Sletten Sletten, Einar Einar
• Is Part Of: Metal-based drugs. Volume 7:Issue 4(2000)
• Page Start: 169
• Page End: 176
• Publication Date: 2000
• Subjects: Metals -- Therapeutic use -- Periodicals; Pharmaceutical chemistry -- Periodicals; Drugs -- Periodicals; Drugs; Metals -- Therapeutic use; Pharmaceutical chemistry; Chemistry, Pharmaceutical -- Periodicals; Metals -- therapeutic use -- Periodicals; Pharmaceutical Preparations -- Periodicals; Periodicals; Electronic journals; 615.23
• DOI: 10.1155/MBD.2000.169
• Languages: English
• ISSNs: 0793-0291

Abstract

Abstract : Recently it has been shown that several analogues of the clinically ineffective trans -DDP exhibit antitumor activity comparable to that of cis -DDP. The present paper describes the binding of antitumor trans -[PtCl2 ( E -iminoether)2 ] ( trans-EE ) to guanosinemonophosphate (GMP) and adenosinemonophosphate (AMP). We have used HPLC and H 1 and N 15 NMR to characterize the different adducts. In the case of a 1:1 mixture of trans-EE and GMP, at an early stage of the reaction, a monofunctional adduct is formed which, subsequently, is partly converted into a monosolvated monofunctional species. After about 70 hours an equilibrium is established between chloro and solvato monofunctional adducts at a ratio of 30/70. In the presence of excess GMP (4:1) the initially formed monofunctional adducts react further to give two bifunctional adducts, one with the iminoether ligands in their original E configurations and the other with the iminoether ligands having one E and the other, Z configurations. The coordination geometry obtained by energy minimization calculations is in qualitative agreement with 2D NMR data.