Tumor-inhibiting ruthenium complexes -formulation and analytical characterization

Abstract

Figure 1 shows the structures of the compounds imidazo l i u m t ra n s-[ t e t ra ch l o ro b i s ( i m i d a zo l e ) ru t h e n at e ( I I I ) ] , HIm t ra n s-[ R u C l 4 ( i m ) 2 ] , and indazo l i u m t ra n s-[ t e t ra ch l o ro b i s ( i n d a zo l e ) ru t h e n at e ( I I I ) ] , HInd t ra n s-[ R u C l 4 ( i n d ) 2 ]. These Ru(III)-complexes exhibited the best results in antitumor tests, as well as in an autochthonous colorectal carcinoma of rats, a model that resembles the colon cancer of humans in its histological ap p e a rance and its behavior against chemotherapeutics [3]. In comparison, the well established antitumor drug Cisplatin, cis-[PtCl 2 (NH 3 ) 2 ], is completely inactive in this model. If one is aware of the high percentage of cancer mortality caused by tumors of the colon and the fact that no satisfactory chemotherapy exists, it is clear that development of these ruthenium-based drugs is of outstanding importance.Although many groups are working on platinum based antitumor drugs since the discovery of the tumor-inhibiting qualities of Cisplatin by Barnett Rosenberg in 1969, a conclusive mode of action has not been found as yet. Even less is known about non platinum antitumor drugs like Ru-complexes and their mode of action. It should be of special interest to enhance knowledge in that field as it might lead to a better understanding of the differences between these metalbased drugs concerning toxicity or selectivity for different tumors. Therefore galenic formulation, hydrolysis reactions, interaction with serum proteins and reactions taking place in

Non-Platinum Chemotherapeutic Metallopharmaceuticals

“…Table summarizes the anticancer activity of a representative selection of ruthenium complexes against animal tumor models. While the activity of [CH 3 CH 2 CO 2 (NH 3 ) 5 Ru](ClO 4 ) 2 suggests that monoacido complexes can be active, multichloro compounds such as cis -[Cl 2 (NH 3 ) 4 Ru]Cl, fac -[Cl 3 (NH 3 ) 3 Ru], , and (HIm) trans -[Cl 4 (Im) 2 Ru] , exhibit the best activity against primary tumors. While fac -[Cl 3 (NH 3 ) 3 Ru] showed good antitumor activity in several tumor screens, its low solubility makes it unsuitable as a drug. , mer -[Cl 3 (tpy)Ru] (tpy = 2,2‘:6‘,2‘-terpyridine) exhibits antitumor activity midway between those of cisplatin and carboplatin in the L1210 cell line and is cytotoxic against human cervix carcinoma HeLa and murine L1210 tumor cell lines.…”

Ruthenium Complexes as Anticancer Agents

“…It should be of special interest to enhance knowledge in that field as it might lead to a better understanding of the differences between these metalbased drugs concerning toxicity or selectivity for different tumors. Therefore galenic formulation, hydrolysis reactions, interaction with serum proteins and reactions taking place in the cell (redox reactions, binding towards DNA, RNA and other occurring target molecules) have been investigated [11]. The obtained results could lead to new improved drugs with enhanced activity and selectivity and reduced side effects.…”

KP1019, A New Redox‐Active Anticancer Agent – Preclinical Development and Results of a Clinical Phase I Study in Tumor Patients

“…Many reports on in vitro interactions of plasma proteins with Ru III complexes were published with regard to the nature and the strength of Ru III -protein adducts [34] [36 -45]. Additionally, the biological consequences of metal -protein adduct formation have been studied [46].…”