Table of Contents
Metal-Based Drugs
Volume 5 (1998), Issue 3, Pages 127-137

In Vivo Nitric Oxide Synthase Inhibitors Can Be Deprived of This Activity: Unexpected Influence of the Tetrachloroplatinate(II) Counteranion. Crystal Structures of Bis(S-Methyl-Isothiouronium)-N,N′-Bis(3-Guanidinopropyl)Piperazinium and Hexamidinium Tetrachloroplatinates(II) Salts

1Laboratoire de Cristallochimie Bioinorganique, Faculté de Pharmacie Paris XI, 5, rue-Baptiste Clément, Châtenay-Malabry, Paris F-92290, France
2Laboratoire de Biochimie, Hôpital Armand Trousseau, Paris, France
3Laboratoire de Chimie Générale, Faculté de Médecine et de Pharmacie, Poitiers, France
4CNRS URA 1534, Laboratoire de Pharmacologie, Hôpital Cochin, Paris, France
5Laboratoire de Chimie Analgtique, Faculté de Pharmacie Paris Xl, Châtenay-Malabry, Paris, France
6Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, Caen, France

Received 12 March 1998; Accepted 25 March 1998

Copyright © 1998 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The synthesis and crystal structures of bis(S-methylisothiouronium) (MSTUH)+, N,N′-bis((3- guanidinopropyl)piperazinium (PipeC3GuaH4)4+ and hexamidinium (HexaH2)2+ tetrachloro platinate(ll) salts ( called hereafter PtMSTU, PtPipeC3Gua and PtHexa respectively ) were investigated. These compounds contain the “amidine” function (- C(=NH)NH2 ) in which the H atoms supplied by the acid have become attached to the imino group of each terminal amidino function. Moreover, in PtPipeC3Gua, the nitrogen atoms of the chair-piperazine moiety are also protonated. The influence of tetrachloroplatinate(ll) counteranion ( versus sulfate, nitrate and diisethionate ) in the in vivo nitrite inhibition by the (MSTUH)+, (PipeC3GuaH4)4+ and (HexaH2)2+ cations was investigated. The three tetrachloroplatinate(ll) salts, unexpectedly, do not inhibit significantly the in vivo nitrite production in comparison with the other salts (sulfate, nitrate and diisethionate and their corresponding previous countercations) which exhibit NO synthase inhibition, especially bis(S-methylisothiouronium) sulfate, a selective and potent inducible NO synthase (iNOS) inhibitor commonly used as standard.