Anticancer Half-Sandwich Rhodium(III) Complexes

Klaudia Máliková,Pavel Štarha,Lukáš Masaryk

doi:10.3390/inorganics9040026

Abstract

Platinum-based anticancer drugs are most likely the most successful group of bioinorganic compounds. Their apparent disadvantages have led to the development of anticancer compounds of other noble metals, resulting in several ruthenium-based drugs which have entered clinical trials on oncological patients. Besides ruthenium, numerous rhodium complexes have been recently reported as highly potent antiproliferative agents against various human cancer cells, making them potential alternatives to Pt- and Ru-based metallodrugs. In this review, half-sandwich Rh(III) complexes are overviewed. Many representatives show higher in vitro potency than and different mechanisms of action (MoA) from the conventional anticancer metallodrugs (cisplatin in most cases) or clinically studied Ru drug candidates. Furthermore, some of the reviewed Rh(III) arenyl complexes are also anticancer in vivo. Pioneer anticancer organorhodium compounds as well as the recent advances in the field are discussed properly, and adequate attention is paid to their anticancer activity, solution behaviour and various processes connected with their MoA. In summary, this work summarizes the types of compounds and the most important biological results obtained in the field of anticancer half-sandwich Rh complexes.

Highlights

Platinum-based drugs have been used for the treatment of various types of cancer for more than 40 years [1]
Platinum-group metals other than Pt are generally accepted as suitable ones for novel anticancer metallodrugs, because a number of Ru, Rh, Pd, Os and Ir complexes have been reported as being highly effective against various types of cancer cells, and importantly, having higher cancer cell selectivity and acting through different mechanisms of action (MoA) than the mentioned Pt(II) drugs [9,10,11,12,13]
Anticancer organorhodium complexes have been in many cases studied together with their Ir(III), Ru(II) and Os(II) analogues, which allowed us to compare compounds differing in the used metal

Summary

Introduction

Platinum-based drugs (e.g., cisplatin; Figure 1) have been used for the treatment of various types of cancer for more than 40 years [1]. The following study showed complex [Rh(η5-Cp*)(pta)Cl2] as ineffective at inhibiting cathepsin B in vitro, which corresponds with the use of its Ir analogue, but differs from effective cathepsin B inhibitors RAPTA-C, its Os congener and NAMI-A [57] Another structurally similar dichlorido Rh complex, [Rh(η5-Cp*)(tcep)Cl2], showed comparable potency with cisplatin in the MDA-MB-231 triple-negative breast cancer cell line, where, this Rh complex was ca one order of magnitude less effective than its Ir counterpart; tcep = tris(2-carboxyethyl)phosphine (Figure 2, Table 1) [31]. Following the pioneering organorhodium complex [Rh(η5-Cp*)(pta)Cl2], several dichlorido complexes of this structural type containing a monodentate N-donor ligand have been reported, but these complexes were less potent in vitro than the clinically used cisplatin [32,33,58,59] Among these complexes, [Rh(η5-Cp*)(npp)Cl2] (Figure 2, Table 1) exhibited higher activity on the MIA-PaCa-2 (pancreatic carcinoma) cells than the Ru and Ir analogues; npp = 2-(1,8-naphthyridin-2-yl)phenol [32]. Complexes with structurally similar thiourea-based ligands achieved lower activity than cisplatin, and in most cases than their co-studied Ru and Ir analogues [61,62]

Chlorido Complexes

Other Types of Monodentate Ligands

Complexes with a Tridentate Ligand

Matallacages

Discussion