Ru(ii)-(PTA) and -mPTA complexes with N2-donor ligands bipyridyl and phenanthroline and their antiproliferative activities on human multiple myeloma cell lines.

Aleksandra Wołoszyn,Giulio Lupidi,Claudio Pettinari,Giorgio Santoni,Gretta Veronica Badillo Patzmay,Massimo Nabissi,Piotr Smoleński,Anna Kwiecień,Riccardo Pettinari

doi:10.1039/c7dt02051a

Abstract

A series of novel ruthenium(ii) 2,2'-bipyridyl (bpy) and 1,10-phenanthroline (phen) derivatives containing PTA (1,3,5-triaza-7-phosphaadamantane) or mPTA (N-methyl-1,3,5-triaza-7-phosphaadamantane cation) have been synthesized and fully characterized. Three types of complexes have been obtained, neutral [Ru(N-N)(PTA)2Cl2] (1, N-N = bpy and 4, N-N = phen), monocationic [Ru(N-N)(PTA)3Cl][Cl] (2, N-N = bpy and 5, N-N = phen) and dicationic [Ru(N-N)(mPTA)Cl2][BF4]2 (3, N-N = bpy and 6, N-N = phen). The solid-state structures of four complexes have been determined by single-crystal X-ray diffraction. The cytotoxicity of the complexes has been evaluated in vitro against U266 and RPMI human multiple myeloma cells.

Highlights

The development of metal anticancer drugs has traditionally focused on cytotoxic platinum compounds only three platinum drugs are today approved for clinical use worldwide and three additional compounds are approved in individual nations
Since Ru complexes were previously found to be effective in U266 and RPMI MM cells,28 we evaluated the cytotoxic effects of new Ru complexes in the same MM cell model, which is a model with a cytogenetic abnormality that in patients is associated with a poor outcome
Water solutions are relatively stable in the range of pH = ±2 in air. These compounds are soluble in other polar solvents, such as DMSO, acetonitrile and DMF

Summary

Introduction

The development of metal anticancer drugs has traditionally focused on cytotoxic platinum compounds only three platinum drugs are today approved for clinical use worldwide and three additional compounds are approved in individual nations. Independent of the nature of the platinum compound used, all platinum drugs are believed to exert their antitumour activity through the same mechanism of action as described for cisplatin. In the search for antitumor drugs with a different spectrum of activity and less side effects than those of platinum drugs, ruthenium compounds appear to be the most promising ones. The development of metal anticancer drugs has traditionally focused on cytotoxic platinum compounds only three platinum drugs are today approved for clinical use worldwide and three additional compounds are approved in individual nations.. In the search for antitumor drugs with a different spectrum of activity and less side effects than those of platinum drugs, ruthenium compounds appear to be the most promising ones. Ruthenium complexes containing polypyridines could combine good water solubility and new electronic properties by introduction of the air-stable and water-soluble aminophosphine, 1,3,5-triaza-7-phosphaadamantane (PTA) or its derivatives into the coordination sphere.. The coordination chemistry of PTA has seen a pronounced development driven by the search for watersoluble transition ruthenium complexes as rather potent antitumor, catalytic or luminescent agents. Ruthenium complexes display antitumor and antimetastatic activity due to their highly tuneable structures, constructable octahedral geometry, redox complexes containing pyridyl ligands are finding numerous applications ranging from imaging or structure- and sitespecific reversible DNA binding agents to therapeutics.

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