Hydroxyquinoline-derived anticancer organometallics: Introduction of amphiphilic PTA as an ancillary ligand increases their aqueous solubility

Abstract

Organometallic compounds based on bioactive ligand systems have shown promising antiproliferative properties. The use of 8-hydroxyquinoline and its derivatives as bioactive ligands resulted in organometallic complexes with potent anticancer activity, but they lack aqueous solubility for further development. We report here the preparation of a series of MII/III(cym/Cp*)Cl complexes (η6-p-cymene (cym): M = Ru, Os; η5-pentamethylcyclopentadienyl (Cp*): M = Rh, Ir) with hydroxyquinoline-derived co-ligands and in a subsequent step the substitution of the chlorido ligands for amphiphilic 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane (PTA). Solubility studies indicated that the introduced PTA ligand significantly improved the aqueous solubility of all complexes. The complexes were shown to be stable in aqueous and DMSO solution over a period of at least 3 d. As would be expected for such modification of complexes, the higher solubility resulted in significantly decreased cytotoxicity in cancer cells. The antiproliferative activity was still more pronounced than that of RAPTA-C [Ru(cym)(PTA)Cl] which, however, has been demonstrated to have antimetastatic and antiangiogenic properties in vivo.