Synthesis of Camptothecin-10-O-glucoside Using an Engineered Oleandomycin Glucosyltransferase

Abstract

Oleandomycin glycosyltransferase variant P67T/S132F/A242V(ASP) was used to convert 10-hydroxy-camptothecin into camptothecin-10-O-glucoside, which was confirmed by spectral analysis. Compared to the pre-viously reported results, the present study reached the conversion rate up to 80% through the optimization of reaction conditions. In addition, compared with 10-hydroxycamptothecin(HCPT), camptothecin-10-O-glucoside inhibited the proliferation of Huh7 cells in a concentration-dependent manner and showed stronger antineoplastic effect but lower toxicity. Furthermore, camptothecin-10-O-glucoside induced more apoptotic cells as compared with the parent compound.

Keywords

Camptothecin-10-O-glucoside / 10-Hydroxycamptothecin / Glycosylation / Glucosyltransferase / Antineoplastic

References

[1] Aiyama R., Nagai H., Nokata K., Shinohara C., Sawada S. Phytochemistry, 1988, 27(2): 3663.

[2] Li D. Z., Zhang Q. Z., Wang C. Y., Zhang Y. L., Li X. Y., Huang J. T., Liu H. Y., Fu Z. D., Song H. X., Lin J. P., Ji T. F., Pan X. D. Eur. J. Med. Chem., 2017, 125(6): 1235.

[3] Wang S., You Y., You Q. D. Chinese Chem. Lett., 2008, 19(8): 918.

[4] Hu W., Zhang C., Fang Y., Lou C. Toxicology In vitro, 2011, 25(9): 513.

[5] Guo Q., Yuan Q. Y. Nat. Prod. Res., 2016, 30(9): 1053.

[6] Ahmed A., Peters N. R., Fitzgerald M. K., Watson J. A., Hoffmann F. M., Thorson J. S. J. Am. Chem. Soc., 2006, 128(12): 14224.

[7] Wilson A. C. Nat. Prod. Rep., 1997, 14(5): 99.

[8] Thorson J. S., Hosted J., Jiang J., Biggins J. B. Ahlert J., Curr. Org. Chem., 2001, 5(10): 139.

[9] Tan Y., Xiao X., Yao J., Han F., Lou H., Luo H. Chem. Res. Chinese Universities, 2017, 33(5): 80.

[10] Quirós L. M., Carbajo R. J., Braña A. F., Salas J. A. J. Biological Chem., 2000, 275(6): 11713.

[11] Gantt R. W., Peltier-Pain P., Thorson J. S. Nat. Prod. Rep., 2011, 28(8): 1811.

[12] Williams G. J., Zhang C., Thorson J. S. Nat. Chem. Biol., 2007, 3(14): 657.

[13] Zhou M., Thorson J. S. Org. Lett., 2011, 13(3): 2786.

[14] Zhou M., Hamza A., Zhan C. G., Thorson J. S. J. Nat. Prod., 2013, 76(16): 279.

[15] Williams G. J., Thorson J. S. Nat. Protoc., 2008, 3(2): 357.

[16] Gantt R. W., Goff R. D., Williams G. J., Thorson J. S. Angew. Chem. Int. Ed., 2008, 47(7): 8889.