Synthesis of New Thiourea-Metal Complexes with Promising Anticancer Properties

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.

Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases

“…Thiourea ligands do not exhibit relevant cytotoxicity in the tested cell lines and the coordination of a metal triggered excellent cytotoxic values in all the cases. The best complex was 134 with IC 50 values of 0.25 ± 0.12 μM against HeLa and 0.70 ± 0.06 μM against Jurkat cells 108 (Fig. 13).…”

Silver Complexes as Anticancer Agents: A Perspective Review

“…The Ag-thiourea complexes 43 and 44 containing phosphine groups were developed and demonstrated their in vitro cytotoxic potential against A549, HeLa and Jurkat cell lines using MTT assay. Complex 43 showed more significant cytotoxicity in HeLa cells, whereas complex 44 showed greater activity against the Jurkat cell line through coordination with phosphorus atom [17].…”

“…Notably, the binuclear silver (I) complexes exhibited a more significant antiproliferation activity in cancer cells than the normal cells and exhibited low toxicity. Based on the reports of recent studies, among various metal complexes, silver metal complexes are more efficient as an anticancer agent in treating various types of cancer, including breast, colorectal, ovarian and lung cancer, compared with cisplatin [17,18]. In this review, only those literature indexed in ScienceDirect, PubMed, Springer, Karger, Molecules, Cross mark and Royal Society of Chemistry databases between 2011 and 2021 were surveyed.…”

Review Artikel: Strategi Pengembangan Senyawa Thiourea Sebagai Agen Antikanker

“…Senyawa-senyawa kompleks thiourea dengan logam terbukti memberikan aktivitas sitotoksik yang tinggi pada sel kanker dibandingkan dengan sel normal yang dibuktikan dibanyak penelitian in vitro dengan berbagai lini sel kanker dan lini sel normal (Plutín et al, 2014;Asghar et al, 2018;Drzewiecka-Antonik et al, 2020;Swaminathan et al, 2021). Pembentukan kompleks thiourea dengan logam telah dibuktikan dapat meningkatkan affinitas ikatan senyawa antikanker dengan DNA sel kanker yang memberikan peningkatan aktivitas sitotoksik dan selektivitas dari senyawa (Plutín et al, 2014;;Pérez et al, 2017;Repich et al, 2017;Yu et al, 2020;Asghar et al, 2018;Canudo-Barreras et al, 2021). Rutenium merupakan logam yang paling banyak dimanfaatkan untuk membentuk kompleks thiourea-logam.…”