Species differences in the renal toxicity of the antiarthritic drug, gold sodium thiomalate

Cheriathundam, Elizabeth; Alvares, Alvito P.

doi:10.1002/(sici)1522-7146(1996)11:4<175::aid-jbt2>3.0.co;2-h

Cited by 10 publications

(3 citation statements)

References 18 publications

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“…This result is extremely positive when compared to the few data reported in the literature related to the renal toxicity induced by gold derivatives. For instance, the antiarthritic drugs auranofin and myochrysine are well known to induce proteinuria and kidney disfunction, 41 and gold nanoparticles are able to penetrate renal cells causing nephrotoxicity. 42 Subsequent histopathological investigations have confirmed the favorable toxicity profile of the tested gold(III) complex.…”

Section: Cancer Therapysupporting

confidence: 73%

Gold(III)‐dithiocarbamato anticancer agents: Activity, toxicology and histopathological studies in rodents

Marzano

Ronconi

Chiara

et al. 2010

Intl Journal of Cancer

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Gold(III)-dithiocarbamato complexes have recently gained increasing attention as potential anticancer agents because of their strong tumor cell growth-inhibitory effects, generally achieved by exploiting non-cisplatin-like mechanisms of action. The rationale of our research work is to combine the antitumor properties of the gold(III) metal center with the potential chemoprotective function of coordinated dithiocarbamates in order to reduce toxic side effects (in particular nephrotoxicity) induced by clinically established platinum-based drugs. In this context, [Au III Br 2 (ESDT)] (AUL12) was proved to exert promising and outstanding antitumor activity in vitro and to overcome both acquired and intrinsic resistance showed by some types of tumors toward cisplatin. As a subsequent extension of our previous work, we here report on detailed in vivo studies in rodents, including antitumor activity toward three transplantable murine tumor models, toxicity, nephrotoxicity and histopathological investigations. Remarkably, the gold(III) complex AUL12 stands out for higher anticancer activity than cisplatin toward all the murine tumor models examined, inducing up to 80% inhibition of tumor growth. In addition, it shows low acute toxicity levels (lethal dose, LD 50 5 30 mg kg 21 ) and reduced nephrotoxicity. Altogether, these results confirm the reliability of our drug design strategy and support the validation of this gold(III)-dithiocarbamato derivative as a suitable candidate for clinical trials.The accidental discovery of the anticancer properties of cisplatin (cis-dichlorodiammineplatinum(II), cis-[Pt II Cl 2 (NH 3 ) 2 ]; Fig. 1) in the mid-1960s 1 has triggered the development of both platinum 2 -and other metal-based 3,4 alternative compounds. Although well-established in current cancer chemotherapy, the use of platinum compounds for the treatment of tumor diseases is massively hampered by severe side effects such as nausea, alopecia, ototoxicity, neurotoxicity, myelosuppression, nephrotoxicity and tumor resistance, either intrinsic or acquired during cycles of therapy. 5 Consequently, the development of novel metallodrugs showing a different pharmacological profile is a major goal of modern medicinal chemistry and drug design.Among the non-platinum antitumor agents, gold complexes have recently gained increasing attention because of their strong inhibitory effects on tumor cell growth, generally achieved by exploiting non-cisplatin-like pharmacodynamic and pharmacokinetic properties and mechanisms of action. 6,7 Owing to their traditional use in medicine for the treatment of rheumatoid arthritis, gold derivatives are suitable candidates as potential alternatives to platinum drugs. In fact, the antiarthritic activity arises from their known immunosuppressive and anti-inflammatory actions, thus establishing, at least in principle, a connection between the two therapies. Moreover, gold(III) complexes show chemical features that are very close to those of clinically established platinum(II) derivatives, such as the pre...

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Section: Cancer Therapysupporting

confidence: 73%

Gold(III)‐dithiocarbamato anticancer agents: Activity, toxicology and histopathological studies in rodents

Marzano

Ronconi

Chiara

et al. 2010

Intl Journal of Cancer

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“…These results are extremely positive when compared to the few data reported in literature related to the renal toxicity induced by gold derivatives. For instance, the goldbased antiarthritic drugs auranofin and myochrysine are well known to give rise to proteinuria and kidney dysfunction [43]. In this context, also the gold nanoparticles, which received great attention in recent years for their potential applications in medicine [44][45][46], proved to have nephrotoxicity as a severe dose-limiting factor because of their ability to penetrate renal cells causing renal damages [47].…”

Section: Toxicological Studiesmentioning

confidence: 99%

Gold(III) Complexes in the Oncological Preclinical Arena: From Aminoderivatives to Peptidomimetics

Nardon¹,

Fregona

2015

CTMC

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In the last decade, we have been developing some gold(III) derivatives showing interesting antitumor properties and reduced systemic and renal toxicity, compared to the clinically-established reference drug cisplatin. Starting from the rationale at the base of our investigations, this review has been divided into two sections, with respect to our patented first- (aminoderivatives) and secondgeneration (peptidomimetics) potential drugs. Every section describes the in vitro and in vivo anticancer activity of the compounds, chosen as models, towards different types of tumor. In particular, we summarize the results achieved so far, in particular taking into account the latest in-depth studies related to their activity, mechanism of action and toxicological profile. Taken together, our data could open up new prospects for further advanced preclinical pharmacological testing.

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“…While, liver injury is a major setback induced by FDA-approved Au I drugs. [34] The potential nephrotoxic and hepatotoxic effects induced by treatment with 7, 2, cisPt, PhB or the combination cisPt: PhB:2 were also evaluated by measuring some specific biomarkers. For kidney injury, the urines of control and treated mice were analyzed for urinary total protein (uTP) and N-acetyl-β-D-glucosaminidase (NAG) (Figure 8A).…”

Section: Reactivity Of the Compounds Towards Cysteine-and Selenocyste...mentioning

confidence: 99%

Oral Anticancer Heterobimetallic Pt^IV−Au^IComplexes Show High In Vivo Activity and Low Toxicity

et al. 2023

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AuI‐carbene and PtIV−AuI‐carbene prodrugs display low to sub‐μM activity against several cancer cell lines and overcome cisplatin (cisPt) resistance. Linking a cisPt‐derived PtIV(phenylbutyrate) complex to a AuI‐phenylimidazolylidene complex 2, yielded the most potent prodrug. While in vivo tests against Lewis Lung Carcinoma showed that the prodrug PtIV(phenylbutyrate)‐AuI‐carbene (7) and the 1 : 1 : 1 co‐administration of cisPt: phenylbutyrate:2 efficiently inhibited tumor growth (≈95 %), much better than 2 (75 %) or cisPt (84 %), 7 exhibited only 5 % body weight loss compared to 14 % for 2, 20 % for cisPt and >30 % for the co‐administration. 7 was much more efficient than 2 at inhibiting TrxR activity in the isolated enzyme, in cells and in the tumor, even though it was much less efficient than 2 at binding to selenocysteine peptides modeling the active site of TrxR. Organ distribution and laser‐ablation (LA)‐ICP‐TOFMS imaging suggest that 7 arrives intact at the tumor and is activated there.

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Species differences in the renal toxicity of the antiarthritic drug, gold sodium thiomalate

Cited by 10 publications

References 18 publications

Gold(III)‐dithiocarbamato anticancer agents: Activity, toxicology and histopathological studies in rodents

Gold(III)‐dithiocarbamato anticancer agents: Activity, toxicology and histopathological studies in rodents

Gold(III) Complexes in the Oncological Preclinical Arena: From Aminoderivatives to Peptidomimetics

Oral Anticancer Heterobimetallic Pt^IV−Au^IComplexes Show High In Vivo Activity and Low Toxicity

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Species differences in the renal toxicity of the antiarthritic drug, gold sodium thiomalate

Cited by 10 publications

References 18 publications

Gold(III)‐dithiocarbamato anticancer agents: Activity, toxicology and histopathological studies in rodents

Gold(III)‐dithiocarbamato anticancer agents: Activity, toxicology and histopathological studies in rodents

Gold(III) Complexes in the Oncological Preclinical Arena: From Aminoderivatives to Peptidomimetics

Oral Anticancer Heterobimetallic PtIV−AuIComplexes Show High In Vivo Activity and Low Toxicity

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Product

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Oral Anticancer Heterobimetallic Pt^IV−Au^IComplexes Show High In Vivo Activity and Low Toxicity