Silver(I) antiproliferative coordination compounds: From structure–activity to structure–selectivity relationships

Over the past decade, a rapidly expanding body of literature has reported structurally diverse silver(I) complexes incorporating a wide range of ligand classes, including N-, O-, S-, and P-donor systems, as well as biologically active scaffolds such as non-steroidal anti-inflammatory drugs, amino acids, and antibiotics. However, despite the wealth of reported cytotoxicity data, direct comparison of biological performance remains challenging due to the heterogeneity of experimental conditions and the frequent absence of systematic selectivity evaluation. In this context, the present review provides a comprehensive and quantitative framework for analyzing the anticancer activity of silver(I) complexes, integrating normalized selectivity descriptors based on global z-score analysis of IC 50 values. This approach enables, for the first time, a statistically robust comparison across structurally diverse systems, facilitating the identification of structure-activity and, critically, structure-selectivity relationships that define the next generation of silver(I)-based anticancer agents.