文献类型： 外文期刊

作者： Shi, Jing-Fang ¹ ; Wu, Ping ² ; Cheng, Xiao-Li ² ; Wei, Xiao-Yi ² ; Jiang, Zi-Hua ³ ;

作者机构： 1.Guangdong Acad Agr Sci, Agrobiol Gene Res Ctr, Guangdong Prov Key Lab Crop Germplasm Resources P, Guangzhou 510640, Peoples R China

2.Chinese Acad Sci, Key Lab Plant Resources Conservat & Sustainable U, South China Bot Garden, Xingke Rd 723, Guangzhou 510650, Peoples R China

3.Lakehead Univ, Dept Chem, 955 Oliver Rd, Thunder Bay, ON P7B 5E1, Canada

关键词： annonaceous acetogenins; squamocin; bullatacin; glycosylated; cytotoxicity; anticancer; solubility

期刊名称：DRUG DESIGN DEVELOPMENT AND THERAPY （ 影响因子：4.162； 五年影响因子：4.278 ）

ISSN： 1177-8881

年卷期： 2020 年 14 卷

页码：

收录情况： SCI

摘要： Background: Annonaceous acetogenins (ACGs) are secondary metabolites produced by the Annonaceae family and display potent anticancer activity against various cancer cell lines. Squamocin and bullatacin are two examples of ACGs that show promising antitumor activity; however, preclinical data are not sufficient partly due to their being highly lipophilic and poorly soluble in water. These compounds also display high toxicity to normal cells. Due to these disadvantageous properties, the therapeutic potential of squamocin and bullatacin as antitumor agents has not been fully evaluated. Methods: In order to enhance their water solubility and potentially improve their cancer targeting, squamocin and bullatacin were conjugated to a glucose or galactose to yield glycosylated derivatives by direct glycosylation or the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction (the click reaction). The synthesized compounds were evaluated for their anticancer property against HeLa, A549 and HepG2 cancer cell lines using MTT assay. Results: Nine glycosyl derivatives were synthesized and structurally characterized. Most of them show comparable in vitro cytotoxicity against HeLa, A549 and HepG2 cancer cell lines as their parent compounds squamocin and bullatacin. It appears that the type of sugar residue (glucose or galactose), the position at which the sugar residue is attached, and whether or not a linking spacer is present do not affect the potency of these derivatives much. The solubility of galactosylated squamocin 13 in phosphate buffer saline (PBS, pH = 7) is greatly improved (1.37 mg/mL) in comparison to squamocin (not detected in PBS). Conclusion: The conjugation of a glucose or galactose to squamocin and bullatacin yields glycosyl derivatives with similar level of anticancer activity in tested cell lines. Further studies are needed to demonstrate whether or not these compounds show reduced toxicity to normal cells and their therapeutic potential as antitumor agents.