Synthesis, characterization, and antileishmanial activity of neutral N-heterocyclic carbenes gold(I) complexes

• Published in: European journal of medicinal chemistry 2018-01, Vol.143, p.1635-1643
• Main Authors: Zhang, Chen, Bourgeade Delmas, Sandra, Fernández Álvarez, Álvaro, Valentin, Alexis, Hemmert, Catherine, Gornitzka, Heinz
• Format: Article
• Language: English
• Subjects: Antileishmanial activity; Chemical Sciences; Coordination chemistry; Gold; J774.1A; Leishmania infantum; N-heterocyclic carbene; Selectivity
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2017.10.060

A series of five new mononuclear neutral gold(I) complexes containing N-heterocyclic carbenes (NHCs) was synthesized and fully characterized by spectroscopic methods. The X-ray structures of four complexes are presented. These gold(I) complexes together with four other neutral gold(I)-NHC complexes previously described were evaluated in vitro against Leishmania infantum promastigotes and axenic amastigotes. Moreover, their cytotoxicity was assessed on the murine macrophages J774A.1. Except one complex (10), eight gold(I)-NHC-Cl complexes show potent activity against the pathological relevant form of L. infantum amastigote with IC50 in the low micromolar and submicromolar range and five of them exhibit a SI close to 10. The lead-complex 11 displays a very high and selective activity (IC50 = 190 nM, SI = 40.29) and constitutes the best promising gold(I)-based drug of this series. [Display omitted] •Mononuclear neutral gold(I) N-heterocyclic carbene complexes as anti-leishmanial agents.•Potent activity in vitro against Leishmania infantum promastigotes and axenic amastigotes.•IC50 values in the low micromolar and submicromolar range against the pathological relevant form of L. infantum.•Selectivity index close to 10 and up to 40 for five complexes.•The lead organometallic drug 12 shows an IC50 = 0.19 μM (amastigotes) with a SI = 40.29.