Synthesis and Antitumor Activity of Amino Acid Ester Derivatives Containing 5-Fluorouracil

Xiong, Jing; Zhu, Haifeng; Zhao, Yajuan; Yun-jun, Lan; Jiang, Jiwang; Yang, Jingjing; Zhang, Shufeng

doi:10.3390/molecules14093142

Cited by 26 publications

(11 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Syntheses and studies of 2 and 3: In addition to 5-FU, which is used as drug model, two new 5-FU prodrugs (2 and 3) with two and three 5-FU units, respectively, linked through an ester function to an alkyl core were synthesized ( Figure 3). These linkers can be cleaved chemically or enzymatically [23,24] to generate 5-FU and/or 5-fluorouracil-acetic acid (5-FUA also referred to as compound 1 in this work) whose biological activities are known. [25] Syntheses: Compounds 2 and 3 were prepared as described in Scheme 1.…”

Section: Resultsmentioning

confidence: 99%

A Designed 5‐Fluorouracil‐Based Bridged Silsesquioxane as an Autonomous Acid‐Triggered Drug‐Delivery System

Giret

Théron

Gallud

et al. 2013

Chemistry A European J

View full text Add to dashboard Cite

Two new prodrugs, bearing two and three 5-fluorouracil (5-FU) units, respectively, have been synthesized and were shown to efficiently treat human breast cancer cells. In addition to 5-FU, they were intended to form complexes through H-bonds to an organo-bridged silane prior to hydrolysis-condensation through sol-gel processes to construct acid-responsive bridged silsesquioxanes (BS). Whereas 5-FU itself and the prodrug bearing two 5-FU units completely leached out from the corresponding materials, the prodrug bearing three 5-FU units was successfully maintained in the resulting BS. Solid-state NMR ((29) Si and (13) C) spectroscopy show that the organic fragments of the organo-bridged silane are retained in the hybrid through covalent bonding and the (1) H NMR spectroscopic analysis provides evidence for the hydrogen-bonding interactions between the prodrug bearing three 5-FU units and the triazine-based hybrid matrix. The complex in the BS is not affected under neutral medium and operates under acidic conditions even under pH as high as 5 to deliver the drug as demonstrated by HPLC analysis and confirmed by FTIR and (13) C NMR spectroscopic studies. Such functional BS are promising materials as carriers to avoid the side effects of the anticancer drug 5-FU thanks to a controlled and targeted drug delivery.

show abstract

Section: Resultsmentioning

confidence: 99%

A Designed 5‐Fluorouracil‐Based Bridged Silsesquioxane as an Autonomous Acid‐Triggered Drug‐Delivery System

Giret

Théron

Gallud

et al. 2013

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…Prior studies have identified that the introduction of an ester function group into the core structure of some plant‐derived anticancer agents such as taxol , camptothecin , bryostatin , and 5‐fluorouracil improved their activity against the usual cell line. Moreover, similar enhancement of the activities is demonstrated in the antiplasmodial and antitrypanosomal activities with bicyclic amides and esters of dialkylamino acids .…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Evaluation of Thalidomide and Phthalimide Esters as Antitumor Agents

Zahran

Abdin

Osman

et al. 2014

Archiv der Pharmazie

View full text Add to dashboard Cite

A series of thalidomide and phthalimide ester analogs were efficiently synthesized from N-chloromethylthalidomide, N-chloromethylphthalimide, and N-(2-bromoethyl)phthalimide derivatives with various biologically important carboxylic acids. The synthesized compounds were purified and characterized by various chromatographic and spectroscopic techniques. The antitumor activity of all the synthesized compounds was screened against human liver and breast cancer cells, which showed that phthalimide ester 6a was the best cytotoxic compound against MCF7 cells, while all of the tested compounds showed a non-cytotoxic effect against HepG2 cells. Compounds 5a, 6a, and 7a possess immunosuppressant effect, while compounds 5c, 5d, 6c, 6d, 7c, and 7d showed an immunostimmulatory effect. Meanwhile, estimation of the binding affinity for all the synthesized compounds toward the vascular endothelial growth factor receptor (VEGFR) showed that compounds 5a, 5b, and 7d were the most potent inhibitors.

show abstract

“…These prodrugs are activated by a biological mediator only when get in specific cells or tissues [4]. 5-FU modifications include conjugation with peptides, amino acids, phospholipids and polymers [5][6][7][8][9]. Among 5-FU prodrugs tegafur, carmofur and floxuridine have already proven their clinical efficacy with low toxicity and increased selectivity and metabolic stability [10].…”

Section: Introductionmentioning

confidence: 99%

5-Fluorouracil derivatives: a patent review (2012 – 2014)

Carrillo

Navarro-Marchal

Ramírez

et al. 2015

Expert Opinion on Therapeutic Patents

View full text Add to dashboard Cite

Although in the past few years there has been a great advancement in the antitumor effectiveness and selectivity of 5-FU-based therapies, it is envisaged that future approaches using 'omics' technologies that could determine the tumor heterogeneity may help in identifying additional candidate genes, microRNAs or cytokines involved in both the path mechanisms of 5-FU-related toxicity and its therapeutic efficacy. Moreover, the development of novel targeted 5-FU derivatives or 5-FU-based therapies tailored to individual patients opens up new possibilities in the improvement of the quality of life and survival for those suffering from this devastating disease.

show abstract

Synthesis and Antitumor Activity of Amino Acid Ester Derivatives Containing 5-Fluorouracil

Cited by 26 publications

References 23 publications

A Designed 5‐Fluorouracil‐Based Bridged Silsesquioxane as an Autonomous Acid‐Triggered Drug‐Delivery System

A Designed 5‐Fluorouracil‐Based Bridged Silsesquioxane as an Autonomous Acid‐Triggered Drug‐Delivery System

Synthesis and Evaluation of Thalidomide and Phthalimide Esters as Antitumor Agents

5-Fluorouracil derivatives: a patent review (2012 – 2014)

Contact Info

Product

Resources

About