Design, Synthesis, and Evaluation of Doxifluridine Derivatives as Nitroreductase-Responsive Anticancer Prodrugs.

Xinmeng Zhang, Taimin Dong, Xu Li, Changjie Xu, Fanghui Chen, Shiben Wang, Xuekun Wang

Abstract read

In one paragraph

Article in Molecules (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

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Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Xinmeng ZhangNational Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China.

Taimin DongNational Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China.

Xu LiNational Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China.

Changjie XuNational Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China.

Fanghui ChenNational Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China.

Shiben WangNational Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China.

Xuekun WangNational Key Laboratory of Macromolecular Drug Development and Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China.ORCID 0000-0002-1457-0050

Funding

Guangyue Young Scholar Innovation Team of Liaocheng University LCUGYTD2022-04Major Project of Research and Development of Shandong Province 2019GSF108226National Natural Science Foundation of China 81803360"Youth Innovation Team Plan" of Shandong Province Higher Education 2022KJ111

6 · The paper itself

Abstract

Antimetabolite antitumor drugs interfere with nucleic acid and DNA synthesis, causing cancer cell death. However, they also affect rapidly dividing normal cells and cause serious side effects. Doxifluridine (5'-deoxy-5-fluorouridine [5'-DFUR]), a 5-fluorouracil (5-FU) prodrug converted to 5-FU by thymidine phosphorylase (TP), exerts antitumor effects. Since TP is distributed in tumor and normal tissues, 5'-DFUR features side effects. Here we designed a series of novel 5'-DFUR derivatives based on high nitroreductase (NTR) levels in the hypoxic microenvironment of tumor tissues by introducing nitro-containing moieties into the 5'-DFUR structure. These derivatives exert their antitumor effects by producing 5-FU under the dual action of TP and NTR in the tumor microenvironment. The derivatives were synthesized and their stability, release, and cytotoxicity evaluated in vitro and antitumor activity evaluated in vivo. Compound

Indexed as

Antineoplastic AgentsDrug DesignFloxuridineNitroreductasesProdrugsAnimalsCell Line, TumorHumansMiceXenograft Model Antitumor AssaysAntineoplastic AgentsdoxifluridineFloxuridineNitroreductasesProdrugsdoxifluridine derivativesnitroreductaseprodrugtumor microenvironment

Identifiers

PMID39519718

DOI10.3390/molecules29215077

PMCPMC11547703

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.