The anti-breast cancer stem cell properties of gold(<scp>i</scp>)-non-steroidal anti-inflammatory drug complexes

Johnson, Alice; Olelewe, Chibuzor; Kim, Jong Hyun; Northcote-Smith, Joshua; Mertens, Randall Tyler; Passeri, Ginevra; Singh, Kuldip; Awuah, Samuel G.; Suntharalingam, Kogularamanan

doi:10.1039/d2sc04707a

Cited by 16 publications

(13 citation statements)

References 76 publications

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“…392 Suntharalingam and co-workers developed gold(I) complexes bearing nonsteroidal anti-inflammatory drugs (NSAID) to target breast cancer stem-cells (Figure 24). 393 Lead complex containing indomethacin moiety showed greater inhibitory effect (80-fold) against breast CSCs than the bulk breast cancer cell population. An inquiry into the mechanism of action of the lead complex revealed cytoplasmic accumulation of the complex, inhibition of cyclooxygenase-2 (COX-2) and increased levels of intracellular ROS.…”

Section: Mitochondrial Targeting Of Gold Complexesmentioning

confidence: 99%

“…This work further demonstrates that targeting CSCs is an effective strategy for cancer treatment. 393 Sun et al also reported a gold(III) meso-tetraphenylporphyrin complex that inhibit formation of spheroids from single cell suspension in U-87 glioblastoma cancer cells. The porphyrin complex demonstrated potent in vitro and in vivo toxicity in a panel of cancer cells and high physiological stability in glutathione and serum albumen.…”

Section: Mitochondrial Targeting Of Gold Complexesmentioning

confidence: 99%

“…In vivo efficacy for the gold(I)-indomethacin complex was demonstrated in 4T1 tumor-bearing mice; tumor was significantly reduced without affecting mice body weight. This work further demonstrates that targeting CSCs is an effective strategy for cancer treatment …”

Section: Therapeutic Gold Complexesmentioning

confidence: 99%

Section: Therapeutic Gold Complexesmentioning

confidence: 99%

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Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

et al. 2023

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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.

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Section: Mitochondrial Targeting Of Gold Complexesmentioning

confidence: 99%

Section: Mitochondrial Targeting Of Gold Complexesmentioning

confidence: 99%

Section: Therapeutic Gold Complexesmentioning

confidence: 99%

Section: Therapeutic Gold Complexesmentioning

confidence: 99%

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Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

et al. 2023

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“…A more recent study demonstrated a multitarget nature of the alkynyl phosphane gold(I) complex by disrupting mitochondrial bioenergetics and glycolysis . Endeavors of using other donor ligands with dual or synergistic activities also emerged recently. − …”

Section: Concept In Gold Drug Designmentioning

confidence: 99%

Modulating the Chemical Reactivity of Gold Complexes in Living Systems: From Concept to Biomedical Applications

2023

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Anti‐Breast Cancer Stem Cell Properties of Silver(I)‐Non‐Steroidal Anti‐Inflammatory Drug Complexes

Singh,

Johnson

et al. 2024

Eur J Inorg Chem

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The synthesis and characterisation of a series of silver(I) complexes (1‐7) containing non‐steroidal anti‐inflammatory drugs (NSAIDs) and triphenylphosphine ligands is reported. The diclofenac‐containing silver(I) complex 1 exhibits micromolar potency towards bulk breast cancer cells and breast cancer stem cells (CSCs) cultured in monolayers. Notably, the silver(I) complex 1 displays up to 9.4‐fold higher potency towards three‐dimensional mammospheres than cisplatin (a clinically used anticancer metallodrug) and salinomycin (a breast‐CSC active small molecule). Mechanistic studies show that the silver(I) complex 1 readily interacts with thiol‐containing biomolecules in solution and elevates intracellular reactive oxygen species levels in breast CSCs. Interestingly the silver(I) complex 1 does not perturb cyclooxygenase‐2 (COX‐2) expression in breast CSCs and its cytotoxicity is unaffected in the presence of prostaglandin E2, implicative of a COX‐2 independent mechanism of action.

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The anti-breast cancer stem cell properties of gold(i)-non-steroidal anti-inflammatory drug complexes

Abstract: 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...

Cited by 16 publications

References 76 publications

Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

Modulating the Chemical Reactivity of Gold Complexes in Living Systems: From Concept to Biomedical Applications

Anti‐Breast Cancer Stem Cell Properties of Silver(I)‐Non‐Steroidal Anti‐Inflammatory Drug Complexes

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