Article

Synthesis and biological evaluation of new 4beta-5-Fu-substituted 4'-demethylepipodophyllotoxin derivatives.

State Key Laboratory of Applied Organic Chemistry & Department of Chemistry, Lanzhou University, Lanzhou, 730000, PR China.
Molecules (Impact Factor: 2.1). 02/2006; 11(11):849-57.
Source: PubMed

ABSTRACT A series of new 4beta-5-Fu-substituted 4'-demethylepipodophyllotoxin derivatives were synthesized and evaluated, together with some previously prepared ones, for their cytotoxic activities against four tumor cell lines (HL60, P388, A549 and BEL7402). Three of these compounds exhibited superior in vitro anticancer activity against P388 and A549 than the reference compound etoposide. In addition, the partition coefficients (P) of all the new and previously synthesized derivatives were determined.

0 Bookmarks
 · 
150 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of novel spin-labeled podophyllotoxin derivatives were synthesized by reacting the corresponding N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxy carbonyl)-amino acids with 4beta-amino-4'-demethylepipodophyllotoxin. The synthesized derivatives 12a-g were evaluated for the partition coefficients, cytotoxicities in vitro against three tumor cell lines (A-549, HL-60, and RPMI-8226) and antioxidative activities in tissues of SD rats by the TBA method. The vast majority of target compounds have shown superior or comparable activities against A-549, HL-60, and RPMI-8226 compared to VP-16, and they have shown more significant antioxidative activities and superior water solubility than VP-16.
    Bioorganic & medicinal chemistry letters 02/2010; 20(3):983-6. DOI:10.1016/j.bmcl.2009.12.048 · 2.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study reports two novel 5-fluorouracil-substituted ampelopsin derivatives. The structures of two new derivatives were characterized by elemental analysis, 1H-NMR, 13C-NMR, IR and MS. Their anticancer activities in vitro against two cancer cell lines, K562 and K562/ADR, were investigated using the MTT assay, and the results showed that the two new compounds were more effective than reference drugs such as ampelopsin and verapamil.
    Molecules 04/2010; 15(4):2114-23. DOI:10.3390/molecules15042114 · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: INTRODUCTION: The fluorinated analog of uracil 5-FU is an antimetabolite, active against a wide range of solid tumors. The main mechanism of action consists in interfering with DNA synthesis and mRNA translation. However, patients treated with 5-FU display several side effects, a result of its nonspecific cytotoxicity for tumor cells. Numerous modifications of the 5-FU structure have been performed in order to overcome these disadvantages. AREAS COVERED: In this review, the metabolic pathways, pharmacokinetics and clinical pharmacology of 5-FU are briefly introduced. Moreover, several derivatives developed and patented, including oral 5-FU prodrugs and combinations with other active compounds, are presented. Finally, new innovative methods for administration and vehiculization of 5-FU and its derivatives are described. EXPERT OPINION: The search for less toxic 5-FU derivatives, which diminish or circumvent some of its disadvantages, has allowed the development of selective antitumor prodrugs and novel methods for tissue-specific drug delivery. Although some of these oral prodrugs are being used clinically, either alone or in combination therapy with other anticancer agents, it seems that the potential of personalized medicine, including pharmacogenomics and targeted therapy with novel 5-FU derivatives, will improve the management and clinical responses of patients treated with 5-FU-based therapy.
    Expert Opinion on Therapeutic Patents 02/2012; 22(2):107-23. DOI:10.1517/13543776.2012.661413 · 3.53 Impact Factor

Preview

Download
1 Download
Available from