Synthesis, characterization and in vitro biological assays of a silver(I) complex with 5-fluorouracil: A strategy to overcome multidrug resistant tumor cells

被引：36

作者：

Bormio Nunes, Julia H. ^{[1
]}

Bergamini, Fernando R. G. ^{[1
]}

Lustri, Wilton R. ^{[2
]}

de Paiva, Paula P. ^{[3
]}

Ruiz, Ana Lucia T. G. ^{[3
]}

de Carvalho, Joao Ernesto ^{[3
,4
]}

Corbi, Pedro P. ^{[1
]}

机构：

[1] Univ Estadual Campinas, Univ Campinas, Dept Inorgan Chem, BR-13083970 Campinas, SP, Brazil

[2] Centro Univ Araraquara, Univ Araraquara, Biotechnol Res Ctr, BR-14801320 Araraquara, SP, Brazil

[3] Univ Estadual Campinas, Univ Campinas, Chem Biol & Agr Pluridisciplinary Res Ctr CPQBA, BR-13148218 Paulinia, SP, Brazil

[4] Univ Estadual Campinas, Univ Campinas, Fac Pharmaceut Sci, BR-13081970 Campinas, SP, Brazil

来源：

JOURNAL OF FLUORINE CHEMISTRY | 2017年 / 195卷

基金：

巴西圣保罗研究基金会;

关键词：

5-Fluorouracil; Silver(I); Metal complex; Antitumor activity; Antibacterial assays; SPECTROSCOPIC CHARACTERIZATION; CRYSTAL-STRUCTURE; ANTIBACTERIAL ASSAYS; ANTICANCER ACTIVITY; CARBENE COMPLEXES; NATURAL-PRODUCTS; SOLID-STATE; CANCER; DNA; DERIVATIVES;

D O I：

10.1016/j.jfluchem.2017.01.016

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

A silver(I) complex with the antitumor drug 5-fluorouracil was synthesized and characterized by a set of chemical and spectroscopic techniques. Elemental, thermogravimetric and mass spectrometric analyses indicate a 3:2 metal/ligand composition, with minimal formula Ag-3(C4HFN2O2)(C4H2FN2O2). Solid-state NMR and IR spectroscopic studies suggest that coordination to silver(I) occurs by the nitrogen atoms N1 and N3, and by oxygen atom 02 of the ligand. The in vitro antiproliferative assays show the higher activity of the silver(I) complex with 5-fluorouracil when compared to the free drug against ovarian multidrug resistant (NCl/ADR-RES) and colon (HT29) tumor cell lines, with 50% growth inhibition (GI(50)) values of 0.36 and 0.34 mu g mL(-1), respectively. Gel electrophoresis assay indicated that the silver(I) complex does not interact with pIRES DNA plasmid. The compound also presented higher activity than cisplatin against a variety of tumor cell lines. The compound was also assayed over Gram-positive (Staphyloccocus aureus) and negative (Escherichia coil and Pseudomonas aeruginosa) bacterial strains and the MIC values show its activity over the considered microorganisms at high concentrations. (C) 2017 Elsevier B.V. All rights reserved.

引用

页码：93 / 101

页数：9

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