Palladium complexes of bidentate pyridine N‐heterocyclic carbenes: Optical resolution, antimicrobial and cytotoxicity studies

Abstract

A series of bidentate pyridine‐functionalized palladium N‐heterocyclic carbene (Pd NHC) complexes with various wingtip substituents (R = methyl, phenyl and tert‐butyl) have been synthesized and evaluated for their potential biomedical applications as antimicrobials and antiproliferative drug candidates. The obtained Pd NHC complexes were applied in a standard broth microdilution assay for determination of their antimicrobial activities against thirteen strains of pathogenic microorganisms. In addition to that, cytotoxic activities of the Pd NHC complexes were also evaluated against three human cancer cell lines, namely breast (MCF‐7), colon (HCT116) and oral (H103) cancer cells, using a standard MTT assay. Upon coordination to palladium, the Pd NHC complexes show significant antimicrobial activities with minimum inhibitory concentrations in the micromolar range, and they are cytotoxic to the tested carcinomas with IC50 ranging from 13 to 38 μM. Evidences for influence of both wingtip substituents and optical isomerism on the biological activities of the complexes have been found.

Antimicrobial and Antifungal Activities of Terpene-Derived Palladium Complexes

“…Specific examples of metallo-complexes demonstrating antimicrobial activity include N-heterocyclic carbene (NHS) complexes of silver and gold, auranofin (a clinically approved antirheumatic drug), colloidal bismuth citrate (CBS, a clinically approved antiulcer drug), and gallium nitrate. On the other hand, although palladium remains less explored in this context, there appears to be growing interest, with a steady number of studies published over the years [14][15][16][17][18][19][20]. Palladium palladacycles have historically garnered attention as anticancer agents due to their potential for diverse coordination geometry and cognate anticancer mechanisms distinct from those of platinum-based therapies such as cis-platin [20].…”

“…This observation suggests that bacterial susceptibility to chemotherapeutic metallo-complexes is significantly influenced by the nature of the coordinated metal ion and its associated coordination sphere. Indeed, in most of the aforementioned studies [14][15][16][17][18][19][20][21], it was found that palladium-derived complexes exhibited significantly higher antibacterial and antifungal activity compared to the corresponding free organic ligands.…”