Nature-Inspired Gold(I) Complexes as Anticancer Agents: Ligand Design, Structure–Activity Relationships, and Mechanisms

TL;DR

This review explores how nature-inspired gold(I) complexes can be designed to improve their anticancer activity and effectiveness compared to traditional drugs.

Contribution

The paper provides a structure–activity perspective on nature-inspired gold(I) complexes for anticancer drug design.

Findings

Nature-inspired ligands enhance the activity and stability of gold(I) complexes.

Heterobimetallic gold complexes show synergistic therapeutic effects.

Gold(I) complexes target enzymes like thioredoxin reductase in cancer cells.

Abstract

Gold complexes have emerged as promising anticancer agents due to their unique chemical properties and alternative mechanisms of action compared to traditional chemotherapy drugs. Their significance lies in their potential to overcome drug resistance and target cancer cells more selectively by targeting enzymes such as thioredoxin reductase, which is overexpressed in several cancer cells. In drug discovery, nature-inspired ligands provide structurally diverse and biologically relevant frameworks that enhance the activity and stability of gold complexes. Recent studies increasingly focus on gold(I) complexes derived from these ligands. In addition, heterobimetallic gold complexes have attracted attention for their synergistic therapeutic effects. Together, these systems represent an important direction in anticancer drug design.

Nature-inspired ligands, including natural product scaffolds and bio-inspired motifs, have emerged as an important source for the development of gold(I) complexes with promising preclinical anticancer activity. This review focuses on structurally characterised gold(I) complexes derived from these ligands, emphasising how ligand structure and gold coordination influence the biological activity. This paper covers the synthesis of nature-inspired gold(I) complexes, alkynyl, N-heterocyclic carbene (NHC), heteroatom-donor, and heterobimetallic complexes, which collectively contribute to enhanced cytotoxicity, stability, and mechanistic diversity. By focusing on these nature-inspired gold(I) complexes, this review provides a concise structure–activity perspective and outlines future opportunities for rational design in anticancer research.

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