Comparison of Free-Hydroxy With 3′,5′-Di-O-Acetyl Ribose of 5-Alkynyl Dicobalt Hexacarbonyl 2′-Deoxy-Furopyrimidines Hybrids: Synthesis, Antiproliferative Activity, and ROS Determination

被引：0

作者：

Kaczmarek, Renata ^{[1
]}

Radzikowska-Cieciura, Ewa ^{[1
]}

Krolewska-Golinska, Karolina ^{[1
]}

Andrei, Graciela ^{[2
]}

Snoeck, Robert ^{[2
]}

Dolot, Rafal ^{[1
]}

Wheeler, Kraig A. ^{[3
]}

Agyei Gyimah, Dominic ^{[4
]}

Yang, Susan ^{[4
]}

Dembinski, Roman ^{[1
,4
]}

机构：

[1] Polish Acad Sci, Ctr Mol & Macromol Studies, Lodz, Poland

[2] Rega Inst, Dept Microbiol Immunol & Transplantat, Leuven, Belgium

[3] Whitworth Univ, Dept Chem, Spokane, WA USA

[4] Oakland Univ, Dept Chem, Rochester, MI 48309 USA

来源：

APPLIED ORGANOMETALLIC CHEMISTRY | 2024年 / 38卷 / 12期

基金：

美国国家卫生研究院;

关键词：

5-alkynylfuropyrimidines; alkynes; anticancer properties; cancer cells; cytotoxicity; dicobalt hexacarbonyl; modified nucleosides; SELECTIVE-INHIBITION; NUCLEOSIDES; POTENT; PYRIMIDINE; ALKYNYL; ANALOGS; FV-100;

D O I：

10.1002/aoc.7695

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Synthesis of 5-alkynyl furopyrimidine nucleoside analogs, with free-ribose groups, was carried out, and their biological activity was evaluated. The substituents introduced at the C-5 included propargyl and homopropargyl alcohols, 4-methylphenyl (p-tolyl), and 4-pentylphenyl substituted alkynyl groups (56%-88%). Subsequently, alkyne function was coordinated to dicobalt hexacarbonyl unit, yielding the corresponding dicobalt hexacarbonyl 5-alkynyl furopyrimidine nucleosides (51%-75%). All compounds contained 4-pentylphenyl group attached at the C-6 position of the bicyclic base, in line with most active antiviral structures. The antiproliferative effect of these modified nucleosides on cancer cells of different phenotypes was determined using in vitro studies. The tested compounds show antiproliferative effects with median inhibitory concentration (IC50) values of 16-23 and 9-15 mu M for HeLa and K562 cells. The determination of reactive oxygen species (ROS) formation in K562 cells in the presence of modified nucleosides may suggest that the mode of action of the examined compounds may be attributed to the induction of oxidative stress.

引用

页数：11