2016
DOI: 10.1021/acs.molpharmaceut.6b00140
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Chemical Reactivity Window Determines Prodrug Efficiency toward Glutathione Transferase Overexpressing Cancer Cells

Abstract: Glutathione transferases (GSTs) are often overexpressed in tumors and frequently correlated to bad prognosis and resistance against a number of different anticancer drugs. To selectively target these cells and to overcome this resistance we previously have developed prodrugs that are derivatives of existing anticancer drugs (e.g., doxorubicin) incorporating a sulfonamide moiety. When cleaved by GSTs, the prodrug releases the cytostatic moiety predominantly in GST overexpressing cells, thus sparing normal cells… Show more

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Cited by 26 publications
(21 citation statements)
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“…ANS-DOX showed to be toxic in GSTA1-1 overexpressing cancer cells. Collectively, these investigations suggested the plausibility of modulating the rate of drug release as well as specifically targeting different GSTs by modifying the sulfonamide moiety 128 .…”
Section: Pro-drugsmentioning
confidence: 94%
See 1 more Smart Citation
“…ANS-DOX showed to be toxic in GSTA1-1 overexpressing cancer cells. Collectively, these investigations suggested the plausibility of modulating the rate of drug release as well as specifically targeting different GSTs by modifying the sulfonamide moiety 128 .…”
Section: Pro-drugsmentioning
confidence: 94%
“…Notably, the less reactive MNS-DOX was more effective in MGST1 overexpressing cells than DNS-DOX. A new derivate of DOX, 4-acetyl-2-nitro-benzenesulfonyl doxorubicin (ANS-DOX) was synthesized and shown to be converted into DOX by MGST1 and GSTA1-1, whereas no activity was observed for GSTP1-1 128 . ANS-DOX showed to be toxic in GSTA1-1 overexpressing cancer cells.…”
Section: Pro-drugsmentioning
confidence: 99%
“…In support of this model, the expression of GSTs is increased in lung cancer portends poor survival and resistance to chemotherapy as well as radiotherapy. Furthermore, GST inhibitors are in development as anticancer agents to modify treatment resistance and shortened survival associated with high GST expression in cancer patients [ 20 ]. All antioxidants are also oxidant at higher concentrations [ 21 , 22 ], thus at high concentrations they can suppress GSTs; this would serve a therapeutic function.…”
Section: Introductionmentioning
confidence: 99%
“… Glutathione transferase overexpressing cancer cells, doxorubicin derivatives in vitro GSTs are often overexpressed and TrxR1 is often upregulated in tumors and frequently correlated to bad prognosis and resistance against a number of different anticancer drugs. These cells could be selectively targeted with drug derivatives, incorporating a sulfonamide moiety (ANS-etoposide, ANS-DOX) [92] . head and neck squamous cell carcinoma, rat model of cisplatin-induced ototoxicity, cisplatin, curcumin in vitro, in vivo Cisplatin has an ototoxic side effect.…”
Section: Oxidative Stress Induced By Conventional Anticancer Therapy mentioning
confidence: 99%
“…Prodrugs have been developed that are derivatives of existing anticancer drugs (etoposide, doxorubicin) incorporating a sulfonamide moiety. With these drugs GSH levels can be decreased and also the redox regulatory enzyme thioredoxin reductase 1 (TrxR1) can be inhibited [92] . Synthetic nitric oxide releasing compounds (e.g.…”
Section: Oxidative Stress Induced By Conventional Anticancer Therapy mentioning
confidence: 99%