2017
DOI: 10.1007/s10637-017-0443-2
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Metabolic carbonyl reduction of anthracyclines — role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents

Abstract: SummaryAnthracycline antibiotics (ANT), such as doxorubicin or daunorubicin, are a class of anticancer drugs that are widely used in oncology. Although highly effective in cancer therapy, their usefulness is greatly limited by their cardiotoxicity. Possible mechanisms of ANT cardiotoxicity include their conversion to secondary alcohol metabolites (i.e. doxorubicinol, daunorubicinol) catalyzed by carbonyl reductases (CBR) and aldo-keto reductases (AKR). These metabolites are suspected to be more cardiotoxic tha… Show more

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Cited by 53 publications
(37 citation statements)
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“…Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic with susbtantial treatment potential in a broad variety of solid neoplasms ( 5 ). The major mechanism underlying the tumor-inhibiting activity of DOX is intercalation into primary double-stranded DNA, which blocks the interaction between DNA and RNA polymerases and results in impaired protein synthesis ( 6 ).…”
Section: Introductionmentioning
confidence: 99%
“…Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic with susbtantial treatment potential in a broad variety of solid neoplasms ( 5 ). The major mechanism underlying the tumor-inhibiting activity of DOX is intercalation into primary double-stranded DNA, which blocks the interaction between DNA and RNA polymerases and results in impaired protein synthesis ( 6 ).…”
Section: Introductionmentioning
confidence: 99%
“…For proteases similar to Mpro, the solute dielectric value that correlates best with experimental results is 4.0 (Sun et al, 2014). Three of the proposed drugs are used in chemotherapy (daunorubicin, amrubicin, and the valrubicin metabolite N-trifluoroacetyladriamycin) (Piska et al, 2017). These drugs as well as meclocycline, a highly toxic antibiotic, should be treated carefully because of side effects in the organism.…”
Section: Discussionmentioning
confidence: 90%
“…Structurally, the lipophilicity properties of VLB are greater than that of doxorubicin which due to the presence of valerate moiety and the trifluoro-acetyl moiety on the amino group of the glycoside, resulting in enhanced intracytoplasmic concentrations [3]. VLB also produces two active metabolites (N-trifluoroacetyl-adriamycin, and Ntrifluoroacetyl-adriamycinol) which is its reduced form [4]. Nowadays, there is high cancer prevalence in modern societies and thus the scrutiny and monitoring of chemotherapy medicines are very important.…”
Section: Introductionmentioning
confidence: 99%