56059-30-4Relevant articles and documents
Synthesis and bio-evaluation of xylan-5-fluorouracil-1-acetic acid conjugates as prodrugs for colon cancer treatment
Sauraj,Kumar, S. Uday,Gopinath,Negi, Yuvraj Singh
, p. 1442 - 1450 (2017)
In the present study, xylan-5-fluorouracil-1-acetic acid (Xyl-5-FUAC) conjugates as colon specific prodrugs were synthesized and evaluated by in-vitro release study. The chemical stability of the conjugates was performed in acidic (pH 1.2) and basic buffers (pH 7.4), which showed their stability in upper gastrointestinal tract. The in-vitro drug release profiles of the conjugates were studied in the presence of rat's gastrointestinal contents. The results showed that the low amounts of drug 3–4% and 5–7% were released in gastric and small intestine contents respectively, while 53–61% of the drug was released in cecum and colonic contents. The cytotoxicity studies of the conjugates were also evaluated on human colorectal cancer cell line (HTC-15 and HT-29), which showed that the conjugates are more cytotoxic than the free drug. Therefore the results reveal that Xyl-5-FUAC conjugates are potential candidates for colon specific drug delivery in the treatment of colonic cancer with minimal undesirable side effects.
Synthesis and evaluation of the 5-fluorouracil-pectin conjugate targeted at the colon
Wang, Qing-Wei,Liu, Xue-Ying,Liu, Li,Feng, Juan,Li, Yu-Hua,Guo, Zhen-Jun,Mei, Qi-Bing
, p. 370 - 379 (2007)
This paper describes the first covalent synthesis of a 5-fluorouracil- pectin (FU-PT) conjugate. This conjugate with the potential for colon-targeted delivery has been evaluated. A sensitive high-performance liquid chromatography (HPLC) method was established for the determination of concentration of 5-FU-1-acetic acid in the gastrointestinal contents and plasma of rats. This method was also used to evaluate the colon-targeting properties of 5-FU-PT. 5-FU-PT was given to rats by oral administration at a dosage of 22.5 mg kg -1. The different parts of gastrointestinal tract and plasma were taken after 1, 3, 5, 7, 9, 12, 24, 36, and 48 h of oral administration of 5-FU-PT to rats, and the concentration of 5-FU-1-acetic acid in gastrointestinal contents and plasma was measured by HPLC. 5-FU-1-acetic acid released from 5-FU-PT was mainly distributed in the cecum and colon. Therefore, the present results suggest that the 5-FU-PT conjugate has a good colon-targeting property.
Synthesis and Evaluation of Neutral Gd(III), Mn(II) Complexes from DTPA-Bisamide Derivative as Potential MRI Contrast Agents
Liao, Zhen-Chuan,Li, Chao-Rui,Yang, Zheng-Yin
, p. 653 - 658 (2016)
A strong chelating ligand was synthesized through the modification of DTPA by bioactive 5-fluorouracil derivatives and characterized by means of mass spectra, Fourier transform infrared spectra, elemental analysis, and nuclear magnetic resonance spectroscopy. Its complexes of Gd(III) and Mn(II) were designed as potential MRI contrast agents. Thermodynamic stability constant of the complexes indicated that they were stable enough to prevent the metal ions from releasing. Relaxivity studies showed that the two complexes provided higher T1-weighted relaxivity than that of commercial contrast agent Gd-DTPA and the Mn(II) complex owned much higher T2-weighted relaxation property. Both the Gd(III) and Mn(II) complexes had the advantage of becoming promising T1-weighted MRI contrast agents.
Preparation and bioactivity assessment of chitosan-1-acetic acid-5-flurouracil conjugates as cancer prodrugs
Mohammed, Mohsin O.,Hussain, Kameran S.,Haj, Nadia Q.
, (2017)
5-fluorouracil (5-FU) is a specific anti-cancer agent that is generally used to treat gastrointestinal, colorectal, and breast cancer. In this work, chitosan (CS) was extracted from local fish scales using an established method. 5-FU was then converted to 1-acetic acid-5-fluorouracil (FUAC) and reacted with this CS to prepare chitosan-1-acetic acid-5-fluorouracil (CS-FUAC) conjugates as a colon-specific prodrug. All compounds were characterized by Proton nuclear magnetic resonance (1H-NMR), Fourier-transforminfrared (FTIR), and UV-visible spectroscopy. The synthesized compound was subjected to a chemical stability study in phosphate buffer (0.2 M, pH 7.4) and in KCl/HCl buffer (0.2 M, pH 1.2) at different time intervals (0-240 min) and incubation at 37 °C. This revealed a significantly greater stability and a longer half-life for the CS-FUAC than for FUAC. Hemolytic activity results indicated a much lower toxicity for CS-FUAC than for 5-FU and supported consideration of CS-FUAC for further biological screening and application trials. The percentage of FUAC in the conjugates was determined by subjecting the prodrug to treatment in basic media to hydrolyze the amide bond, followed by absorbency measurements at 273 nm. The cytotoxicity studies of the conjugates were also evaluated on human colorectal cancer cell line (HT-29), which showed that the conjugates are more cytotoxic than the free drug. Therefore, CS-FUAC conjugates can be considered to represent potential colon-specific drug delivery agents, with minimal undesirable side effects, for colon cancer therapy.
5-Fluorouracil acetic acid/β-cyclodextrin conjugates: Drug release behavior in enzymatic and rat cecal media
Udo, Koichi,Hokonohara, Kazuhiro,Motoyama, Keiichi,Arima, Hidetoshi,Hirayama, Fumitoshi,Uekama, Kaneto
, p. 95 - 100 (2010)
5-Fluorouracil-1-acetic acid (5-FUA) was prepared and covalently conjugated to β-cyclodextrin (β-CyD) through ester or amide linkage, and the drug release behavior of the conjugates in enzymatic solutions and rat cecal contents were investigated. The 5-FUA/β-CyD ester conjugate was slowly hydrolyzed to 5-FUA in aqueous solutions (half lives (t1/2) = 38 and 17 h at pH 6.8 and 7.4, respectively, at 37 °C), whereas the amide conjugate was hardly hydrolyzed at these physiological conditions, but hydrolyzed only in strong alkaline solutions (>0.1 M NaOH) at 60 °C. Both ester and amide conjugates were degraded in solutions of a sugar-degrading enzyme, α-amylase, to 5-FUA/maltose and triose conjugates, but the release of 5-FUA was only slight in α-amylase solutions. In solutions of an ester-hydrolyzing enzyme, carboxylic esterase, the ester conjugate was hydrolyzed to 5-FUA at the same rate as that in the absence of the enzyme, whereas the amide conjugate was not hydrolyzed by the enzyme. On the other hand, 5-FUA was rapidly released when the ester conjugate was firstly hydrolyzed by α-amylase, followed secondly by carboxylic esterase. The results indicated that the ester conjugate was hydrolyzed to 5-FUA in a consecutive manner, i.e. it was firstly hydrolyzed to the small saccharide conjugates, such as the maltose conjugate, by α-amylase, and the resulting small saccharide conjugates having less steric hindrance was susceptible to the action of carboxylic esterase, giving 5-FUA. The in vitro release behavior of the ester conjugate was clearly reflected in the hydrolysis in rat cecal contents and in the in vivo release after oral administration to rats.
A novel pH-sensitive (±)-α-tocopherol-5-fluorouracil adduct with antioxidant and anticancer properties
Li, Dong-Wei,Tian, Fang-Fang,Ge, Yu-Shu,Ding, Xin-Liang,Li, Jia-Han,Xu, Zi-Qiang,Zhang, Mei-Fang,Han, Xiao-Le,Li, Ran,Jiang, Feng-Lei,Liu, Yi
, p. 10713 - 10715 (2011)
A novel pH-sensitive (±)-α-tocopherol-5-fluorouracil (VE-5-FU) adduct with antioxidant and anticancer properties for antioxidant-based cancer chemoprevention was synthesized and utilized for selective drug release in the stomach.
A novel 5-fluorouracil prodrug using hydroxyethyl starch as a macromolecular carrier for sustained release
Luo, Qing,Wang, Puxiu,Miao, Yuqiang,He, Haibing,Tang, Xing
, p. 2642 - 2647,6 (2012)
The objective of this study was to develop a sustained-release drug delivery system for 5-fluorouracil (5- FU) to improve its short half-life. 5-Fluorouracil-1-acetic acid (FUAC) was prepared and then conjugated to hydroxyethyl starch (HES) through ester bonds. The conjugates were relatively stable in acidic buffer solution at pH 5.8 and slowly released FUAC but became more sensitive to hydrolysis with an increase in the pH and temperature. The conjugates were degraded to FUAC both in human and rat plasma with halftime life of 20.4 h and 24.6 h, respectively. Both 5-FU and FUAC were released in a rat liver homogenate following a 12 h incubation of the conjugates. The pharmacokinetic behavior was evaluated in rats after intravenous injection of 5-FU, FUAC and the conjugates. The drug release data in vitro and in vivo indicated that HES is a promising carrier for the sustained-release of antitumor drugs.
A designed 5-fluorouracil-based bridged silsesquioxane as an autonomous acid-triggered drug-delivery system
Giret, Simon,Theron, Christophe,Gallud, Audrey,Maynadier, Marie,Gary-Bobo, Magali,Garcia, Marcel,Wonga Chia Man, Michel,Carcel, Carole
, p. 12806 - 12814 (2013)
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 ( 29Si and 13C) spectroscopy show that the organic fragments of the organo-bridged silane are retained in the hybrid through covalent bonding and the 1Ha 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 13Ca 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. My name is Bond, H-Bond: A new 5-fluorouracil (5-FU) prodrug, showing cytotoxicity against breast cancer cells, was successfully maintained through H-bonds to an organobridged silsesquioxane (BS). The resulting complex is not affected under physiological conditions but operates under lysosomal pH to deliver the prodrug (see figure). The designed 5-FU prodrug/BS is a promising autonomous pH-sensitive material carrier, which avoids the side effects of the anticancer drug due to a controlled and targeted release. Copyright
Synthesis, characterization and DNA binding investigations of a new binuclear Ag(I) complex and evaluation of its anticancer property
Bigdeli, Fahime,Gao, Lan-Xing,Hu, Mao-Lin,Morsali, Ali,Wu, Deng-Ze,Yan, Xiao-Wei,Zheng, Mian-Hong
, p. 953 - 964 (2020)
Aim: A new Ag(I) complex (A3) was synthesized and evaluated for its anticancer activity against human cancer cell lines. Materials and Methods: The complex A3 was characterized by1 H,13 C, and31P nuclear magnetic resonance (NMR), infrared (IR) spectra, elemental analysis, and X-ray crystallography. The interaction of the complex with CT-DNA was studied by electronic absorption spectra, fluorescence spectroscopy, and cyclic voltammetry; cell viability (%) was assessed by absorbance measurement of the samples. Results: The interaction mode of the complex A3 with DNA is electrostatic, and this complex shows good potential in anticancer properties against HCT 116 (human colorectal cancer cells) and MDA-MB-231 (MD Anderson-metastatic breast) cell lines with 0.5 micromolar concentrations. Conclusion: The Ag(I) complex could interact with DNA noncovalently and has anticancer properties.
A novel brain targeted 5-FU derivative with potential antitumor efficiency and decreased acute toxicity: Synthesis, in vitro and in vivo evaluation
Chen, Hui,Wu, Wenqi,Li, Yanping,Gong, Tao,Sun, Xun,Zhang, Zhirong
, p. 271 - 276 (2014)
The broad-spectrum antitumor agent 5-fluorouracil (5-FU), has been used to treat various solid malignant tumors. However, its short life-time in vivo and poor ability to cross the blood-brain barrier has limited its application to brain tumor therapy. In
