Physicochemical Studies and Anticancer Potency of Ruthenium η⁶-p-Cymene Complexes Containing Antibacterial Quinolones

Abstract

With the aim of exploring the anticancer properties of organometallic compounds with bioactive ligands, Ru(arene) compounds of the antibacterial quinolones nalidixic acid (2) and cinoxacin (3) were synthesized, and their physicochemical properties were compared to those of chlorido(η6-p-cymene)(ofloxacinato-κ2O,O)ruthenium(II) (1). All compounds undergo a rapid ligand exchange reaction from chlorido to aqua species. 2 and 3 are significantly more stable than 1 and undergo minor conversion to an unreactive [(cym)Ru(μ-OH)3Ru(cym)]+ species (cym = η6-p-cymene). In the presence of human serum albumin 1−3 form adducts with this transport protein within 20 min of incubation. With guanosine 5′-monophosphate (5′-GMP; as a simple model for reactions with DNA) very rapid reactions yielding adducts via its N7 atom were observed, illustrating that DNA is a possible target for this compound class. A moderate capacity of inhibiting tumor cell proliferation in vitro was observed for 1 in CH1 ovarian cancer cells, whereas 2 and 3 turned out to be inactive.

Synthesis of moxifloxacin–Au (III) and Ag (I) metal complexes and their biological activities

“…These complexes are highly soluble in dimethylformamide (DMF). Therefore, these metal chelates are dissolved in DMF to perform conductivity measurements (El-Megharbel et al 2015;Kljun et al 2011;Khairnar and Singh 2016). A known amount of solid complex was transferred into 25 ml standard flask and dissolved in DMF.…”

Solution equilibrium studies of anticancer ruthenium(II)-η6-p-cymene complexes of pyridinecarboxylic acids

“…These comprise picolinic acid, thiomaltol, thioallomaltol, etc. [26,[29][30][31][32][33][34][35]. The type of chelating ligands does not only have an influence on the biological properties but also impacts the stability of the complex formed by preventing hydrolysis of the Ru(II)( 6 -p-cymene) organometallic fragment.…”

New method for the speciation of ruthenium-based chemotherapeutics in human serum by conjoint liquid chromatography on affinity and anion-exchange monolithic disks

“…Chlorido(Á 6 -p-cymene)(nalidixicato-Ä 2 O,O)Ru(II) (1) was synthesised and characterised according to procedures described by Kljun et al [39]. The (H 2 im)[trans-Ru(III)Cl 4 (Him) 2 ] (2; KP418) was generously provided by the Institute of inorganic chemistry at the University of Vienna.…”

“…Therefore, the aim of the present work was to apply CLC on affinity and anion-exchange monolithic disks for speciation of Ru-based chemotherapeutics in human serum, using UV detection to follow the separation of serum proteins and ID-ICP-MS for quantification of separated Ru species. Two Ru compounds with tumour-inhibiting properties, namely ruthenium quinolone complex, chlorido(Á 6 -p-cymene)(nalidixicato-Ä 2 O,O)Ru(II) (1), which is a newly synthesised compound [39] and (H 2 im)[transRu(III)Cl 4 (Him) 2 ] (2; KP418) [40,41] that is currently undergoing preclinical studies, were investigated. The potential of the CLC monolithic chromatography for investigating the kinetics of Rudrug interactions with serum proteins was compared with the speciation data obtained for serum samples spiked with cisplatin.…”