The
gold drugs, gold sodium thiomalate (Myocrisin), aurothioglucose
(Solganal), and the orally administered auranofin (Ridaura), are utilized
in modern medicine for the treatment of inflammatory arthritis including
rheumatoid and juvenile arthritis; however, new gold agents have been
slow to enter the clinic. Repurposing of auranofin in different disease
indications such as cancer, parasitic, and microbial infections in
the clinic has provided impetus for the development of new gold complexes
for biomedical applications based on unique mechanistic insights differentiated
from auranofin. Various chemical methods for the preparation of physiologically
stable gold complexes and associated mechanisms have been explored
in biomedicine such as therapeutics or chemical probes. In this Review,
we discuss the chemistry of next generation gold drugs, which encompasses
oxidation states, geometry, ligands, coordination, and organometallic
compounds for infectious diseases, cancer, inflammation, and as tools
for chemical biology via gold–protein interactions. We will
focus on the development of gold agents in biomedicine within the
past decade. The Review provides readers with an accessible overview
of the utility, development, and mechanism of action of gold-based
small molecules to establish context and basis for the thriving resurgence
of gold in medicine.
The anti-breast cancer stem cell (CSC) properties of a series of gold(I) complexes comprising of various non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine 1-8 are reported. The most effective gold(I)-NSAID complex...
Emerging synthetic development of chiral gold(III) complexes has prompted new opportunities in catalysis and material science with limited utility in biomedicine. Here, we demonstrate potential chemotherapeutic capability of [C^N]Au(III)Cl(R-DuPhos)] (1-7)...
The preparation
of cyclometalated complexes offers a path to stable
materials, catalysts, and therapeutic agents. Here, we explore the
anticancer potential of novel biphenyl organogold(III) cationic complexes
supported by diverse bisphosphine ligands, Au-1–Au-5, toward aggressive glioblastoma and triple negative breast cancer
cells (TNBCs). The [C^C] gold(III) complex, Au-3, exhibits
significant tumor growth inhibition in a metastatic TNBC mouse model.
Remarkably, Au-3 displays promising blood serum stability
over a relevant therapeutic window of 24 h and alteration in the presence
of excess L-GSH. The mechanism-of-action studies
show that Au-3 induces mitochondrial uncoupling, membrane
depolarization, and G1 cell cycle arrest and prompts apoptosis. To
the best of our knowledge, Au-3 is the first biphenyl
gold-phosphine complex to uncouple mitochondria and inhibit TNBC growth
in vivo.
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