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 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.
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 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.
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.
Syntheses, structural, and biological studies of two new peptide compounds, 2(s)-(5-fluorouracil-1-aceto)amino-2-isopropyl acetate hemihydrate and 2(s)-(5-fluorouracil-1-aceto)amino-2-isopropyl acetic acid
Hu, Mao-Lin,Yin, Ping,Ma, Zhi-Cheng,Morsali, Ali
, p. 807 - 813 (2008)
Two new peptide compounds, 2(s)-(5-fluorouracil-1-aceto)amino-2-isopropyl acetate hemihydrate (1:1/2H2O) and 2(s)-(5-fluorouracil-1-aceto) amino-2-isopropyl acetic acid (2), have been synthesized and characterized by elemental analysis, IR, su
Two new Cu (II) complexes based on 5-fluorouracil-1-yl acetic acid and N-donor ligands: Investigation of their interaction with DNA and anticancer activity
Xi, Yun-Hong,Yan, Xin,Bigdeli, Fahime,Zhang, Qianwen,Esrafili, Leili,Hanifehpour, Younes,Zhang, Wei-Bing,Hu, Mao-Lin,Morsali, Ali
, (2021/09/22)
Two new Cu (II) complexes [Cu (bpy)2L1] BF4.CH3OH (Z3) and [Cu (phen)2L1] BF4·H2O (Z9), L1 = 5-Fluorouracil-1-yl Acetic Acid, were synthesized based on 5-Fluorouracil-1-yl Acetic
Preliminary SAR and biological evaluation of potent HIV-1 protease inhibitors with pyrimidine bases as novel P2 ligands to enhance activity against DRV-resistant HIV-1 variants
Zhu, Mei,Ma, Ling,Zhou, Huiyu,Dong, Biao,Wang, Yujia,Wang, Zhen,Zhou, Jinming,Zhang, Guoning,Wang, Juxian,Liang, Chen,Cen, Shan,Wang, Yucheng
, (2019/11/28)
Introducing pyrimidine bases, the basic components of nucleic acid, to P2 ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitors because of the carbonyl and amino groups promoting the formation of extensive hydrogen bonding interactions. In this work, we provide evidence that inhibitor 10e, with N-2-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide as the P2 ligand and a 4-methoxylphenylsulfonamide as the P2′ ligand, displayed remarkable enzyme inhibitory and antiviral activity, with the IC50 2.53 nM in vitro and a promising inhibition ratio with 68% against wild-type HIV-1 in vivo, with low cytotoxicity. This inhibitor also exhibited appreciable antiviral activity against DRV-resistant HIV-1 variants, which was of great value for further study.
Electrophilic addition to the multiple bond of 1-carboxymethyl-5-fluorouracil
Chernikova, I. B.,Mustaphin, A. G.,Yunusov, M. S.
, p. 114 - 117 (2020/04/21)
1-Carboxymethyl-5-fluoro-5-halogeno-6-hydroxy-5,6-dihydrouracils and 1-carboxymethyl- 5-fluoro-6-hydroxy-5-nitro-5,6-dihydrouracil were synthesized in high yields by oxidative halogenation or nitration of 1-carboxymethyl-5-fluorouracil. Oxidative halogenation or nitration of 5-fluoro-1-(methoxycarbonylmethyl)uracil in acidic media results in the addition of the corresponding groups at the C(5) atom of uracil and simultaneous hydrolysis of the ester group. Bimolecular ions of the obtained compounds were detected in the negative ion mass spectra.
