Abstract：
:Malignant tumor cells have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential antitumor therapy. In this study, the 7-ethyl-10-boronic acid camptothecin (B1) was synthesized for the first time as prodrug of SN-38, by linking a cleavable aryl carbon-boron bond to the SN-38. Prodrug B1 selectively activated by H2O2, converted rapidly to the active form SN-38 under favorable oxidative conditions in cancer cells with elevated levels of H2O2. The cell survival assay showed that prodrug B1 was equally or more effective in inhibiting the growth of six different cancer cells, as compared to SN-38. Unexpectedly, prodrug B1 displayed even more potent Topo I inhibitory activity than SN-38, suggesting that it was not only a prodrug of SN-38 but also a typical Topo I inhibitor. Prodrug B1 also demonstrated a significant antitumor activity at 2.0 mg/kg in a xenograft model using human brain star glioblastoma cell lines U87MG.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Wang L,Xie S,Ma L,Chen Y,Lu Wdoi
10.1016/j.ejmech.2016.03.063subject
Has Abstractpub_date
2016-06-30 00:00:00pages
84-89eissn
0223-5234issn
1768-3254pii
S0223-5234(16)30246-Xjournal_volume
116pub_type
杂志文章abstract：:The synthesis and photophysical parameters of two novel isosteric cationic zinc(II) phthalocyanines: 2,9(10),16(17),23(24)-tetrakis[(N-butyl-N-methylammoniumethylsulfanyl]phthalocyaninatozinc(II) tetraiodide (6) and 2,9(10),16(17),23(24)-tetrakis[(N-dibutyl-N-methylammonium)ethoxy]phthalocyaninatozinc(II) tetraiodide ...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
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abstract：:Infections caused by Enterococcus faecalis (Ef) represent nowadays a relevant health problem. We selected Thymidylate synthase (TS) from this organism as a potential specific target for antibacterial therapy. We have previously demonstrated that species-specific inhibition of the protein can be achieved despite the re...
journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.02.006
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journal_title：European journal of medicinal chemistry
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abstract：:Indazoles is an important class of heterocyclic compounds having a wide range of biological and pharmaceutical applications. There is enormous potential in the synthesis of novel heterocyclic systems to be used as building blocks for the next generation of pharmaceuticals as anti-bacterial, anti-depressant and anti-in...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
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abstract：:Herein we report the design, synthesis, bioinformatic and biological studies of benzimidazole and benzothiophene derivatives as new cannabinoid receptor ligands. To test the hypothesis that the lack of a hydrogen bond interaction between benzimidazole and benzothiophene derivatives with Lys192 reduces their affinity f...
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.06.004
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abstract：:ATX was capable of catalyzing the hydrolysis of LPC to the lipid mediator LPA which attracted considerable attention on the development of potent ATX inhibitors. Herein, driven by the HTS product indole-based lead 1, a hybridization strategy was utilized to construct the trifluoroacetyl hydrazone moiety through assemb...
journal_title：European journal of medicinal chemistry
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更新日期：2020-09-01 00:00:00
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journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.12.005
更新日期：2015-01-27 00:00:00
