Reductive activation of 5-fluorodeoxyuridine prodrug possessing azide methyl group by hypoxic X-irradiation

Tanabe, Kazuhito; Ishizaki, Jin; Ando, Yumiko; Itô, Takeo; Nishimoto, Sei‐ichi

doi:10.1016/j.bmcl.2011.12.106

Cited by 18 publications

(8 citation statements)

References 22 publications

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“…In addition, azide moiety has been widely used as a scaffold to design new chemical entities for anti-proliferation 21 – 26 and arylazide derivatives have been shown to be potent antitumor agents. For example, trans -2,3-dimethoxycinnamoyl azide derivative 1 (Fig.…”

Section: Introductionmentioning

confidence: 99%

Structure-Activity Relationship Studies of β-Lactam-azide Analogues as Orally Active Antitumor Agents Targeting the Tubulin Colchicine Site

Liu

et al. 2017

Sci Rep

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We have synthesized a series of new β-lactam-azide derivatives as orally active anti-tumor agents by targeting tubulin colchicine binding site and examined their structure activity relationship (SAR). Among them, compound 28 exhibited the most potent antiproliferative activity against MGC-803 cells with an IC50 value of 0.106 μM by induction of G2/M arrest and apoptosis and inhibition of the epithelial to mesenchymal transition. 28 acted as a novel inhibitor of tubulin polymerization by its binding to the colchicine site. SAR analysis revealed that a hydrogen atom at the C-3 position of the β-lactam was required for the potent antiproliferative activity of β-lactam-azide derivatives. Oral administration of compound 28 also effectively inhibited MGC-803 xenograft tumor growth in vivo in nude mice without causing significant loss of body weight. These results suggested that compound 28 is a promising orally active anticancer agent with potential for development of further clinical applications.

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Section: Introductionmentioning

confidence: 99%

Structure-Activity Relationship Studies of β-Lactam-azide Analogues as Orally Active Antitumor Agents Targeting the Tubulin Colchicine Site

Liu

et al. 2017

Sci Rep

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“…Prodrugs are pharmacologically inactive compounds that require activation via metabolic conversion [16], allowing control of where, when and how much drug activity occurs [17]. This is particularly important for chemotherapeutic drugs, where the active drug ideally only acts on tumor cells in order to reduce toxic side effects [18].…”

Section: Introductionmentioning

confidence: 99%

Polymorphic Cytochrome P450 Enzymes (CYPs) and Their Role in Personalized Therapy

et al. 2013

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The cytochrome P450 (CYP) enzymes are major players in drug metabolism. More than 2,000 mutations have been described, and certain single nucleotide polymorphisms (SNPs) have been shown to have a large impact on CYP activity. Therefore, CYPs play an important role in inter-individual drug response and their genetic variability should be factored into personalized medicine. To identify the most relevant polymorphisms in human CYPs, a text mining approach was used. We investigated their frequencies in different ethnic groups, the number of drugs that are metabolized by each CYP, the impact of CYP SNPs, as well as CYP expression patterns in different tissues. The most important polymorphic CYPs were found to be 1A2, 2D6, 2C9 and 2C19. Thirty-four common allele variants in Caucasians led to altered enzyme activity. To compare the relevant Caucasian SNPs with those of other ethnicities a search in 1,000 individual genomes was undertaken. We found 199 non-synonymous SNPs with frequencies over one percent in the 1,000 genomes, many of them not described so far. With knowledge of frequent mutations and their impact on CYP activities, it may be possible to predict patient response to certain drugs, as well as adverse side effects. With improved availability of genotyping, our data may provide a resource for an understanding of the effects of specific SNPs in CYPs, enabling the selection of a more personalized treatment regimen.

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“…14,15 X-ray induced photodynamic therapy was also demonstrated in cells, 16 and small molecule prodrugs were converted to small molecule anti-cancer drugs in cells by X-rays. 17,18 We wish to show here that a specially designed NDC can allow triggered release of drug molecules in cancer cells under X-ray irradiation. This is the first demonstration of increased cytotoxicity from X-ray triggered release of chemotherapeutic drugs from NDC in cells.…”

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confidence: 99%

X-ray triggered release of doxorubicin from nanoparticle drug carriers for cancer therapy

et al. 2013

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Reductive activation of 5-fluorodeoxyuridine prodrug possessing azide methyl group by hypoxic X-irradiation

Cited by 18 publications

References 22 publications

Structure-Activity Relationship Studies of β-Lactam-azide Analogues as Orally Active Antitumor Agents Targeting the Tubulin Colchicine Site

Structure-Activity Relationship Studies of β-Lactam-azide Analogues as Orally Active Antitumor Agents Targeting the Tubulin Colchicine Site

Polymorphic Cytochrome P450 Enzymes (CYPs) and Their Role in Personalized Therapy

X-ray triggered release of doxorubicin from nanoparticle drug carriers for cancer therapy

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