Synthesis of New Thiourea-Metal Complexes with Promising Anticancer Properties.

Guillermo Canudo-Barreras,M Concepción Gimeno,Isabel Marzo,Lourdes Ortego,Raquel P Herrera,Anabel Izaga

doi:10.3390/molecules26226891

Guillermo Canudo-Barreras, M Concepción Gimeno + Show 4 more

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https://doi.org/10.3390/molecules26226891

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Abstract

In this work, two thiourea ligands bearing a phosphine group in one arm and in the other a phenyl group (T2) or 3,5-di-CF3 substituted phenyl ring (T1) have been prepared and their coordination to Au and Ag has been studied. A different behavior is observed for gold complexes, a linear geometry with coordination only to the phosphorus atom or an equilibrium between the linear and three-coordinated species is present, whereas for silver complexes the coordination of the ligand as P^S chelate is found. The thiourea ligands and their complexes were explored against different cancer cell lines (HeLa, A549, and Jurkat). The thiourea ligands do not exhibit relevant cytotoxicity in the tested cell lines and the coordination of a metal triggers excellent cytotoxic values in all cases. In general, data showed that gold complexes are more cytotoxic than the silver compounds with T1, in particular the complexes [AuT1(PPh3)]OTf, the bis(thiourea) [Au(T1)2]OTf and the gold-thiolate species [Au(SR)T1]. In contrast, with T2 better results are obtained with silver species [AgT1(PPh3)]OTf and the [Ag(T1)2]OTf. The role played by the ancillary ligand bound to the metal is important since it strongly affects the cytotoxic activity, being the bis(thiourea) complex the most active species. This study demonstrates that metal complexes derived from thiourea can be biologically active and these compounds are promising leads for further development as potential anticancer agents.

Highlights

Cancer is one of the leading causes of death in the world [1]
The synthesis of thiourea ligands bearing a phosphine moiety has been carried out with the purpose to study the coordination modes with Au and Ag metal atoms and check the suitability of the final complexes as anticancer drugs. The differences among both metal centers in terms of coordination geometries has allowed the preparation of linear gold complexes, with the metal only bonded to the phosphorus atom, or trigonal planar and tetrahedral silver complexes with the ligand coordinated as PS chelate
The thiourea ligands and their complexes were explored by the MTT assay against different cancer cell lines (HeLa, A549 and Jurkat)

Summary

Introduction

Cancer is one of the leading causes of death in the world [1]. Due to the continued necessity to combat this mortal illness, the number of research groups that has focused their studies on this area is very wide. Antitumor compounds that show cytotoxicity and genotoxicity in these treatments can alter healthy cells causing very important side effects [2]. These undesired effects can limit the effectiveness of the treatments. For this reason, the development of selective antitumor agents has become a great challenge in last decades. Metal-based drugs have been widely used for chemotherapeutic treatments in certain types of cancer. Cisplatin and other Pt derivatives have been clinically used in several cancer types [3,4,5]. Ruthenium complexes are already being studied and some of them are in clinical trials [10,11]

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