Novel Gold Complexes with Nitrogen Acyclic Carbenes and their Applications as Anticancer Agents

Gold drugs are well known and have been widely studied for their potential chemotherapeutic properties in anticancer treatments, although they have some limitations as for example chemical stability.^1,2

Gold N-heterocyclic carbenes are excellent s-donor ligands and forms extraordinarily stable gold derivatives, and indeed NHC-Au(I) species display high cytotoxicity in vitro (low micromolar to nanomolar) against a variety of human cancer cell lines with different degrees of selectivity. In the search for new alternatives of stable and robust derivatives, not only N-heterocyclic but N-acyclic carbenes could be explored. ^2,3,4

N-acyclic carbenes are easily accessible via the reaction between isocyanide gold compounds and different amines (Scheme 1). The reaction between one of those derivatives with different thiol groups, in presence of K₂CO₃, as deprotonating agent, has led to a family of gold(I) NAC thiolate derivatives with high cytotoxicity (Scheme 2).

Scheme 1- Reactions between isocyanide gold(I) compounds and different amines.

Scheme 2 - Reaction between compound 4 and different thiol derivatives.

Biological activity was measured by the MTT assay for different human cancer cell lines: A-549 (lung cancer) and MiaPaca2 (pancreatic cancer) for the different synthetized compounds, calculating their IC₅₀. The IC₅₀ values found are in the very low micromolar range and this means an excellent start point for future the development of these compounds as anticancer drugs.

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¹ B. Bertrand, A. Casini, Dalton Trans., 2014, 43, 4209.

² B. Bertrand, A. Citta, I. L. Franken, M. Picquet, A. Folda, V. Scalcon, M. P. Rigobello ,  P. Le Gendre, A. Casini, E. Bodio. J. Biol. Inorg. Chem., 2015, 20, 1005–1020.

³ O. Dada, D. Curran, C. O'Beirne, H. Müller-Bunz, X. Zhu, M. Tacke. J. Organomet. Chem. 2017, 840, 30-37.

⁴ W. Liu, R. Gust.  Coord. Chem. Revs., 2016, 329, 191-213.