Design and synthesis of enantiopure NHC-silver(I) and -gold(I) complexes with anticancer, anti-inflammatory and antioxidant properties

Abstract

So far, several interesting reports dealing with N-Heterocyclic Carbene (NHC) complexes bearing silver and gold have been published, highlighting the versatility of them in several research fields and their various applications, as well. However, most of the reported NHC complexes have been synthetically obtained and studied as racemate, whereas less is still known about the properties of enantiopure complexes. Aiming at contributing to fill this gap, herein a new series of enantiopure NHC complexes of silver(I) and gold(I) bearing an imidazole derivative, opportunely substituted, with one or two asymmetric carbons has been synthesized. These complexes have been characterized by 1H and 13C NMR, mass spectrometry, and elemental analysis and studied for their anticancer, anti-inflammatory and antioxidant properties. The most active complex was also further investigated for its ability in modulating two main enzymes involved in cancer and inflammatory diseases, viz. human Topoisomerase I (hTopoI) and murine Inducible Nitric Oxide synthase (iNOS). The outcomes highlight the role of the configuration and substituents in the regulation of the above-mentioned targets, strengthening the need to widen the studies on enantiopure NHC complexes, which may represent useful compounds to be further developed for the obtaining of tailored therapeutic regimens.