Syntheses and anticancer activities of novel glucosylated (−)-epigallocatechin-3-gallate derivatives linked via triazole rings

Bo-Ya Shi,Xuan-Jun Wang,Jun Sheng,Ze-Hao Wang,Xiu-Li Sun,Hao-Nan Yang,Cheng-Ting Zi,Yi-Long Wu,Yin-Rong Xie,Ning Zhang

doi:10.1007/s00044-021-02726-5

Bo-Ya Shi, Xuan-Jun Wang + Show 8 more

Open Access

https://doi.org/10.1007/s00044-021-02726-5

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Abstract

Novel glucosylated (-)-epigallocatechin-3-gallate derivatives 10–13 having the EGCG analogs conjugated to the d-glucosyl azide were synthesized by carrying out the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, and were evaluated for their cytotoxicities against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) using MTT assays. Compounds 10 and 11 showed the highest levels of cytotoxicity against the HL-60 cells with IC50 values of 4.57 and 3.78 μM, respectively, and showed moderate selectivity toward cancer cell lines. Compound 11 was also shown to induce apoptosis in HL-60 cells. Most notably, inclusion of the perbutyrylated glucose residue in an EGCG derivative was concluded to lead to increased anticancer activity.

Highlights

The novel triazole-linked glucose-(-)-epigallocatechin-3-gallate derivatives 10 – 13 were synthesized according to the synthetic route shown in Scheme 1
2,3,4,6-tetra-O-butyryl-1-azido-α-Dglucopyranose 7 was readily prepared from D-glucose by using a method similar to that reported in the literature [26]
The synthesized compounds 12 and 13 were further analyzed using 2D-NMR spectroscopy (Fig. 2); the heteronuclear multiple bond correlation (HMBC) of compound 12 showed a strong correlation between C12′-H (5.11 ppm) and C-4′ (139.4 ppm) of the D ring

Summary

Introduction

The major catechins in green tea including (-)-epicatechin (EC, 1), (-)epicatechin-3-gallate (ECG, 2), (-)-epigallocatechin (EGC, 3) and (-)-epigallocatechin-3-gallate (EGCG, 4) (Figure 1) have been reported to display numerous biological activities [4,5,6]. EGCG is the most abundant catechin found in green tea and has been reported to display physiological activities stronger than those of the other catechins [7,8,9] and to display many types of biological activities including anti-oxidative, anti-inflammatory, anti-cancer, anti-infection and neuroprotective activities [10,11,12]. We reported the syntheses and cytotoxicities of glucosylated EGCG derivatives, we found that, in aqueous solution, EGCG glucosides displayed higher activities against cells of human breast cancer cell lines and higher levels of stability than did EGCG [21]. Chemical informatics analyses of these compounds were carried out, and the chemical properties of the compounds were correlated with their anticancer activity

Results And Discussion

Conclusion

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