Synthesis and Activity Evaluation of Novel Prenylated Flavonoids as Antiproliferative Agents

doi:10.1007/s40242-018-8013-5

高等学校化学研究 ›› 2018, Vol. 34 ›› Issue (4): 564-570.doi: 10.1007/s40242-018-8013-5

Synthesis and Activity Evaluation of Novel Prenylated Flavonoids as Antiproliferative Agents

Kingsadingthongkham VONGDETH^1,2, RAN Liqiong¹, YAN Lili¹, WANG Qiuan¹

1. College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China;
2. Department of Chemistry, Faculty of Natural Sciences, National University of Laos, Vientiane P. O. BOX 7322 Lao P. D. R

收稿日期:2018-01-12 出版日期:2018-08-01 发布日期:2018-05-07
通讯作者: WANG Qiuan E-mail:wangqa@hnu.edu.cn
基金资助:
Supported by the National Natural Science Foundation of China(Nos.J1210040, 21173074).

Synthesis and Activity Evaluation of Novel Prenylated Flavonoids as Antiproliferative Agents

Kingsadingthongkham VONGDETH^1,2, RAN Liqiong¹, YAN Lili¹, WANG Qiuan¹

1. College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China;
2. Department of Chemistry, Faculty of Natural Sciences, National University of Laos, Vientiane P. O. BOX 7322 Lao P. D. R

Received:2018-01-12 Online:2018-08-01 Published:2018-05-07
Contact: WANG Qiuan E-mail:wangqa@hnu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China(Nos.J1210040, 21173074).

摘要/Abstract

摘要： Twenty prenylated flavonoids 1-20 were synthesized by glycoside hydrolysis, dehydrogenation, selective O-methylation, O-prenylation and Claisen rearrangement reaction, from abundant and inexpensive natural flavonoids naringin, hespiredin, quercetin and myricetin. Among them, 1-7, 10-15 and 17-20 are novel compounds, the natural product 3,3',4',7-tetramethoxy-8-prenyl-5-hydroxy flavonoid(16) was synthesized in a high yield. Their antiprolirative activities were evaluated in vitro on a panel of three human cancer cell lines(HeLa, HCC1954 and SK-OV-3). The results show that most of the target compounds displayed moderate to potent antiprolirative activities against the three cancer cells with half maximal inhibitory concentration(IC₅₀) values from 0.49 μmol/L to 95.07 μmol/L. Among them, 3',4',7-trimethoxyl-5-hydroxyl-8-prenyl flavonoid(12) exhibited the strongest antiprolirative activity against the three cancer cells mentioned above with IC₅₀ values of 0.91-7.08 μmol/L. 3',7-Dimethoxy-5-O-prenyl flavone(6) and 3',4',7-trimethoxy-5-O-prenyl flavone(10) showed selective antiproliferative activity against HCC1954 cells with IC₅₀ value of 0.49 and 5.32 μmol/L, respectively.

关键词: Prenylated flavonoid, Claisen rearrangement, Antiproliferative activity, Cancer cell

Abstract: Twenty prenylated flavonoids 1-20 were synthesized by glycoside hydrolysis, dehydrogenation, selective O-methylation, O-prenylation and Claisen rearrangement reaction, from abundant and inexpensive natural flavonoids naringin, hespiredin, quercetin and myricetin. Among them, 1-7, 10-15 and 17-20 are novel compounds, the natural product 3,3',4',7-tetramethoxy-8-prenyl-5-hydroxy flavonoid(16) was synthesized in a high yield. Their antiprolirative activities were evaluated in vitro on a panel of three human cancer cell lines(HeLa, HCC1954 and SK-OV-3). The results show that most of the target compounds displayed moderate to potent antiprolirative activities against the three cancer cells with half maximal inhibitory concentration(IC₅₀) values from 0.49 μmol/L to 95.07 μmol/L. Among them, 3',4',7-trimethoxyl-5-hydroxyl-8-prenyl flavonoid(12) exhibited the strongest antiprolirative activity against the three cancer cells mentioned above with IC₅₀ values of 0.91-7.08 μmol/L. 3',7-Dimethoxy-5-O-prenyl flavone(6) and 3',4',7-trimethoxy-5-O-prenyl flavone(10) showed selective antiproliferative activity against HCC1954 cells with IC₅₀ value of 0.49 and 5.32 μmol/L, respectively.

Key words: Prenylated flavonoid, Claisen rearrangement, Antiproliferative activity, Cancer cell

Kingsadingthongkham VONGDETH, RAN Liqiong, YAN Lili, WANG Qiuan. Synthesis and Activity Evaluation of Novel Prenylated Flavonoids as Antiproliferative Agents[J]. 高等学校化学研究, 2018, 34(4): 564-570.

Kingsadingthongkham VONGDETH, RAN Liqiong, YAN Lili, WANG Qiuan. Synthesis and Activity Evaluation of Novel Prenylated Flavonoids as Antiproliferative Agents[J]. Chemical Research in Chinese Universities, 2018, 34(4): 564-570.

参考文献

[1] Raffa D., Maggio B., Raimondi M. V., Plescia F., Daidone G., Eur. J. Med. Chem., 2017, 142, 213
[2] Verma A. K., Pratap R., Tetrahydron, 2012, 68(41), 8523
[3] Vogel S., Ohmayer S., Brunner G., Heilmann J., Bioorg. Med. Chem., 2008, 16(8), 4286
[4] Lei Q., Zhang S., Liu M., Li J., Zhang X., Long Y., Mol. Divers., 2017, 21(4), 957
[5] Dong X., Liu Y., Yan J., Jiang C., Chen J., Liu T., Hu Y., Bioorg. Med. Chem., 2008, 16(17), 8151
[6] Neves M. P., Cidade H., Pinto M., Silva A. M. S., Gales L., Damas A. M., Lima R.T., Vasconcelos M. H., Nascimento M. S. J., Eur. J. Med. Chem., 2011, 46(6), 2562
[7] Wen Z., Zhang Y., Wang X., Zeng X., Hu Z., Liu Y., Xie Y., Liang G., Zhu J., Luo H., Xu B., Eur. J. Med. Chem., 2017, 133, 227
[8] Basabe P., de Roman M., Marcos I. S., Diez D., Blanco A., Bodero O., Mollinedo F., Eur. J. Med. Chem., 2010, 45(9), 4258
[9] Wang C., Wu P., Shi J. F., Jiang Z. H., Wei X. Y., Eur. J. Med. Chem., 2015, 100, 139
[10] Jung A. H., Jin E. S., Choi J. R., Manh T. H., Kim S. Y., Min S. B., Son K. Y., Ahn R. B., Kim W. B., Sohn S. S., Choi S. J., Arch. Pharm. Res., 2011, 34(12), 2087
[11] Zhang B., Duan D., Ge C., Yao J., Liu Y., Li X., Fang J., J. Med. Chem., 2015, 58(4), 1795
[12] Chen M., Shi L., Tang J., Wang Q. A., Chem. Res. Chinese Universities, 2016, 32(5), 754
[13] Nguyen V. S., Li W., Li Y., Wang Q. A., Med. Chem. Res., 2017, 26, 1585
[14] Nguyen V. S., Shi L., Wang S. C., Wang Q. A., Anti-cancer Agents Med. Chem., 2017, 17(1), 137
[15] Liu J. D., Chen L., Cai S. L., Wang Q. A., Carbohyd. Res., 2012, 357, 41
[16] Wu Z., Cai S. L., Fan W. J., Wang Q. A., Chin. J. Org. Chem., 2012, 32(7), 1296
[17] Ou L., Han S., Ding W., Che Z., Ye Z., Yang H., Zhang G., Lou Y., Chen J., Yu Y., Mol. Divers., 2011, 15(3), 665
[18] Pinhey J. T., Southwell I. A., Aust. J. Chem., 1973, 26(2), 409
[19] Song Y. P., Xin Z. Y., Wan Y. M., Li J. B., Ye B. P., Xue X. W., Eur. J. Med. Chem., 2015, 90, 695

Synthesis and Activity Evaluation of Novel Prenylated Flavonoids as Antiproliferative Agents

Synthesis and Activity Evaluation of Novel Prenylated Flavonoids as Antiproliferative Agents

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