Expanding on the plecstatin anticancer agent class: exchange of the chlorido ligand for N-heterocyclic ligands.

Autor: Kumar, Saawan, Riisom, Mie, Jamieson, Stephen M. F., Söhnel, Tilo, Bhargava, Suresh, Sun, Jing, Hartinger, Christian G.
Zdroj: Australian Journal of Chemistry; 2024, Vol. 77 Issue 9, p1-7, 7p
Abstrakt: Metal piano-stool complexes based on pyridinecarbothioamide (PCA) have shown promising antiproliferative and in vivo anticancer activity, in particular [Ru(cym)(p -F-PCA)Cl]PF6 (cym is η 6- p -cymene; plecstatin-1). The impact of modifications of the PCA and π-bound ligands on biological properties has been extensively investigated. Herein, we explored the influence of exchanging the chlorido ligand with the N -heterocycles 1-methylimidazole, 1-methylbenzimidazole and pyridine. In solution, an equilibrium between the protonated and deprotonated forms of the thioamide bond was observed, which was found dictated by the solvent system with both species detected in polar solvents. [Ru(cym)(PCA)Cl]+ complexes exhibit unique behaviour in an aqueous environment where they rapidly form dimeric species after substitution of the chlorido ligand for the sulfur donor of the PCA ligand of a second complex molecule. This was also observed for the synthesised complexes with the N -heterocyclic ligands being cleaved from the Ru centre allowing for dimerisation, which may be reversed by acidification of the solution resulting in the formation of equivalent mononuclear compounds. This behaviour explains the similar biological properties of the complexes with respect to that of plecstatin-1. Replacing the chlorido ligand in [Ru(η 6- p -cymene)(p -fluoropyridinecarbothioamide)Cl]PF6 with the N -heterocycles 1-methylimidazole, 1-methylbenzimidazole and pyridine gave complexes with similar antiproliferative activities in human cancer cells at low micromolar concentrations. This can be explained by dimerisation in aqueous solution and formation of the same di-Ru complexes after cleaving of the chlorido or N -heterocycle ligands. (Image credit: Saawan Kumar.) This article belongs to the 10th Anniversary Collection of RACI and AAS Award papers. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje