Semisynthesis and cytotoxicity evaluation of a series of ocotillol type saponins and aglycones from 20(S)-ginsenoside Rg₂, Rh₁, protopanaxatriol and their 20(R)-epimers

Abstract

With the oxidation treatment, eighteen compounds were separated from 20(S)-ginsenoside Rg₂, Rh₁, protopanaxatriol(PPT) and their 20(R)-epimers in total and cytotoxicity of most of them was evaluated against three human cancer cell lines HeLa, A549 and MCF-7 by 3-(4,5-dimetylthiazol-z-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. Their structures were confirmed by means of nuclear magnetic resonance(NMR) and mass spectrometry and the results were compared with those of previous literature. In this study, we systematically semisynthesized all four ocotillol type saponins, i.e., (20S, 24S), (20S, 24R), (20R, 24S) and (20R, 24R). All the configurations at C20 kept the same with their starting materials. Meanwhile a pair of C24 epimers was generated in terms of ocotillol type saponins. In addition, seven compounds(4―8, 13 and 14) were reported firstly. The cytotoxic results distinguished the ocotillol type products(6, 7, 13 and 14) from 20(R)-PPT and 20(R)-ginsenoside Rh₁, which possessed better cytotoxicities than their correspondents from 20(S)-epimers against HeLa cells, and the carbonyl group at C3 can improve the cytotoxicity, which helped us to gain deeper insight into Ocotillol type saponins.

Keywords

Semisynthesis / Ocotillol / Saponin / Cytotoxicity

References

[1] Dou D., Chen Y., Ren J., Pei Y., Chen Y. J. Chin. Pharm. Sci., 2002, 11(4): 119.

[2] Fujita S., Kasai R., Ohtani K., Yamasaki K., Chiu M. H., Nie R. L., Tanaka O. Phytochemistry, 1995, 38(2): 465.

[3] Li Q., Yao Z. H., Shi Y. H., Liu X., Yao X. S., Ye W. C. Molecules, 2007, 12(4): 907.

[4] Simirgiotis M. J., Jimenez C., Rodriguez J., Giordano O. S., Tonn C. E. J. Nat. Prod., 2003, 66(12): 1586.

[5] Nagai M., Tanaka N., Tanaka O., Ichikawa S. Chem. Pharm. Bull., 1973, 21(9): 2061.

[6] Yu C., Fu F., Yu X., Han B., Zhu M. Arzneimittel Forsch., 2007, 57(9): 568.

[7] Zhou Z., Ma C., Zhang H., Bi Y., Chen X., Tian H., Xie X., Meng Q., Lewis Peter J., Xu J. Eur. J. Med. Chem., 2013, 68: 444.

[8] Wang Z. J., Sun L., Peng W., Ma S., Zhu C., Fu F., Heinbockel T. Neuroscience, 2011, 195: 1.

[9] Konoshima T., Takasaki M., Tokuda H., Nishino H., Duc N. M., Kasai R., Yamasaki K. Biol. Pharm. Bull., 1998, 21(8): 834.

[10] Stavrianidi A. N., Rodin I. A., Braun A. V., Stekolshchikova E. A., Shpigun O. A. J. Anal. Chem., 2014, 69(14): 1323.

[11] Li X. G., Zhang L. X., Meng X. Y., Hou J. R., Zhang J. J. Jilin Agr. Univ., 2005, 27(6): 645.

[12] Bi Y., Wang T., Meng Q. G., Zhang J., Wang L., Li Q., Zhao F., Sun H. Rec. Nat. Prod., 2012, 6(3): 242.

[13] Bi Y., Tian J., Ji C., Zhang J., Wang N., Jiang N., Sun H., Meng Q. G. J. Med. Plants Res., 2011, 5(31): 6731.

[14] Meng Q. G., Tan W. J., Hou G. G., Zhang X. Y., Hu X. Y., Yang F., Bai G. J., Zhu W. W., Cai Y., Bi Y., J. Mol. Struct., 2013, 1054/1055, 1

[15] Meng Q. G., Yi B., Liang W., Jiang N., Jiang Y., Zhang J., Yi S., Sun H. Lett. Org. Chem., 2011, 8(9): 682.

[16] Kasai R., Hara K., Dokan R., Suzuki N., Mizutare T., Yoshihara S. I., Yamasaki K. Chem. Pharm. Bull., 2000, 48(8): 1226.

[17] Li L., Chen X., Li D., Zhong D. Drug Metab. Dis., 2011, 39(3): 472.

[18] Wang X., Sakuma T., Asafu A. E., Shiu G. K. Anal. Chem., 1999, 71(8): 1579.

[19] Gu X. Q., Chen Y. P., Hu T. T., Lu X. H., Li X. Q., Du X. H., Cao X., Wang W. H., Xu Z. G. Chem. Res. Chinese Universities, 2011, 27(4): 584.

[20] Xu J., Sun C., Zhuang G., Zhao H. J. Shenyang Pharm. Univ., 2011, 28(9): 712.

[21] Li P., Liu J. Semisynthetic Method and Pharmaceutical Application of Pseudoginsenoside(Pdq), 2005.

[22] Nguyen M. D., Kasai R., Ohtani K., Ito A., Nguyen T. N., Yamasaki K., Tanaka O. Chem. Pharm. Bull., 1994, 42(3): 634.

[23] Tanaka O., Morita T., Kasai R., Kinouchi J., Sanada S., Ida Y., Shoji J. Chem. Pharm. Bull., 1985, 33(6): 2323.

[24] Liu J. P., Tian X., Liu H. Y., Zhang Q. H., Lu D., Li P. Y., Zhao C. F. J. Asian Nat. Prod. Res., 2013, 15(9): 974.

[25] Nguyen M. D., Nguyen T. N., Kasai R., Ito A., Yamasaki K., Tanaka O. Chem. Pharm. Bull., 1993, 41(11): 2010.

[26] Wang J. R., Yau L. F., Zhang R., Xia Y., Ma J., Ho H. M., Hu P., Hu M., Liu L., Jiang Z. H. J. Agr. Food Chem., 2014, 62(12): 2558.

[27] Usami Y., Liu Y. N., Lin A. S., Shibano M., Akiyama T., Itokawa H., Morris-Natschke S. L., Bastow K., Kasai R., Lee K. H. J. Nat. Prod., 2008, 71(3): 478.

[28] Fujita S., Kasai R., Ohtani K., Yamasaki K., Chiu M. H., Nie R. L., Tanaka O. Phytochemistry, 1995, 39(3): 591.