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DOI: 10.1055/s-0042-110858
Phenylethylchromones with In Vitro Antitumor Promoting Activity from Aquilaria filaria
Publikationsverlauf
received 10. April 2016
revised 02. Juni 2016
accepted 15. Juni 2016
Publikationsdatum:
08. Juli 2016 (online)
![](https://www.thieme-connect.de/media/plantamedica/20170304/lookinside/thumbnails/10-1055-s-0042-110858_pma0291-1.jpg)
Abstract
A new chromone, 2-(2-hydroxy-2-phenylethyl)chromone (1), was isolated together with ten known phenylethyl chromones from MeOH extracts of agarwood (Aquilaria filaria). The selected compounds were evaluated in an antiproliferative assay against five human tumor cell lines, including a multidrug-resistant cell line. They were also tested for antitumor promoting activity, as mediated by 12-O-tetradecanoylphorbol-13-acetate-induced activation of the Epstein-Barr virus early antigen in Raji cells. Among all compounds, 4′,7-dimethyoxy-6-hydroxychromone (2) displayed broad spectrum antiproliferative activity against all tumor cell lines tested with IC50 values of 25–38 µM, while 8 was selectively inhibitory against multidrug-resistant cells. All tested compounds suppressed tumor promotion at noncytotoxic concentrations. 4′,6-Dihydroxyphenylethylchromone (7) exhibited the most potent effect with an IC50 value of 319 mol ratio relative to 12-O-tetradecanoylphorbol-13-acetate. This study is the first to report the antitumor promoting activity of 2-(2-phenylethyl)chromone derivatives, as well as the selective antiproliferative activity of 8 against a multidrug-resistant tumor cell line.
Key words
agarwood - Aquilaria filaria (Oken) Merr. - Thymelaeaceae - 2-(2-phenylethyl)chromone - antitumor promoting activity - antiproliferative activity-
References
- 1 Wang T, Li LF, Zhang K, Zhang WY, Pei YH. New 2-(2-phenylethyl)chromones from Bothriochloa ischaemum . J Asian Nat Prod Res 2001; 3: 145-149
- 2 Yoon JS, Lee MK, Sung SH, Kim YC. Neuroprotective 2-(2-phenylethyl)chromones of Imperata cylindrica . J Nat Prod 2006; 69: 290-291
- 3 Ibrahim SR. New 2-(2-phenylethyl)chromone derivatives from the seeds of Cucumis melo L var. reticulatus . Nat Prod Commun 2010; 5: 403-406
- 4 Dai HF, Liu J, Han Z, Zeng YB, Wang H, Mei WL. Two new 2-(2-phenylethyl)chromones from Chinese eaglewood. J Asian Nat Prod Res 2010; 12: 134-137
- 5 Gao YH, Liu JM, Lu HX, Wei ZX. Two new 2-(2-phenylethyl)chromen-4-ones from Aquilaria sinensis (Lour.) Gilg. Helv Chim Acta 2012; 95: 951-954
- 6 Liu J, Wu J, Zhao YX, Deng YY, Mei WL, Dai HF. A new cytotoxic 2-(2-phenylethyl)chromone from Chinese eaglewood. Chin Chem Lett 2008; 19: 934-936
- 7 Hashimoto K, Nakahara S, Inoue T, Sumida Y, Takahashi M, Masada Y. A new chromone from agarwood and pyrolysis products of chromone derivatives. Chem Pharm Bull 1985; 33: 5088-5091
- 8 Shimada Y, Tominaga T, Konishi T, Kiyosawa S. Studies on the agarwood (Jinko). I. Structures of 2-(2-phenylethyl)chromone derivatives. Chem Pharm Bull 1982; 30: 3791-3795
- 9 Yagura T, Shibayama N, Ito M, Kiuchi F, Honda G. Three novel diepoxy tetrahydrochromones from agarwood artificially produced by intentional wounding. Tetrahedron Lett 2005; 46: 4395-4398
- 10 Yang L, Qiao L, Xie D, Yuan Y, Chen N, Dai J, Guo SX. 2-(2-Phenylethyl)chromones from Chinese eaglewood. Phytochemistry 2012; 76: 92-97
- 11 Okudera Y, Ito M. Production of agarwood fragrant constituents in Aquilaria calli and cell suspension cultures. Plant Biotechnol 2009; 26: 307-315
- 12 Chen D, Xu Z, Chai X, Zeng K, Jia Y, Bi D, Ma Z, Tu P. Nine 2-(2-phenylethyl)chromone derivatives from the resinous wood of Aquilaria sinensis and their inhibition of LPS-induced NO production in RAW 264.7 cells. Eur J Org Chem 2012; 2012: 5389-5397
- 13 Wu B, Kwon SW, Hwang GS, Park JH. Eight new 2-(2-phenylethyl)chromone (= 2-(2-phenylethyl)-4H-1-benzopyran-4-one) derivatives from Aquilaria malaccensis agarwood. Helv Chim Acta 2012; 95: 1657-1665
- 14 Li W, Cai CH, Dong WH, Guo ZK, Wang H, Mei WL, Dai HF. 2-(2-Phenylethyl)chromone derivatives from Chinese agarwood induced by artificial holing. Fitoterapia 2014; 98: 117-123
- 15 Liao G, Mei WL, Dong W, Li W, Wang P, Kong FD, Gai CJ, Song XQ, Dai HF. 2-(2-Phenylethyl)chromone derivatives in artificial agarwood from Aquilaria sinensis . Fitoterapia 2016; 110: 38-43
- 16 Konishi T, Konoshima T, Shimada Y, Kiyosawa S. Six new 2-(2-phenylethyl)chromones from agarwood. Chem Pharm Bull (Tokyo) 2002; 50: 419-422
- 17 Yang DL, Mei WL, Zeng YB, Guo ZK, Zhao YX, Wang H, Zuo WJ, Dong WH, Wang QH, Dai HF. 2-(2-Phenylethyl)chromone derivatives in Chinese agarwood “Qi-Nan” from Aquilaria sinensis . Planta Med 2013; 79: 1329-1334
- 18 Yang DL, Wang H, Guo ZK, Dong WH, Mei WL, Dai HF. A new 2-(2-phenylethyl)chromone derivative in Chinese agarwood ʼQi-Nanʼ from Aquilaria sinensis . J Asian Nat Prod Res 2014; 16: 770-776
- 19 Yagura T, Ito M, Kiuchi F, Honda G, Shimada Y. Four new 2-(2-phenylethyl)chromone derivatives from withered wood of Aquilaria sinensis . Chem Pharm Bull (Tokyo) 2003; 51: 560-564
- 20 Hoye TR, Jeffrey CS, Shao F. Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons. Nat Protoc 2007; 2: 2451-2458
- 21 Takasaki M, Konoshima T, Kozuka M, Tokuda H. Anti-tumor promoting activities of euglobals from Eucalyptus plants. Biol Pharm Bull 1995; 18: 435-438
- 22 Nakagawa-Goto K, Yamada K, Taniguchi M, Tokuda H, Lee KH. Cancer preventive agents 9. Betulinic acid derivatives as potent cancer chemopreventive agents. Bioorg Med Chem Lett 2009; 19: 3378-3381
- 23 Hung HY, Nakagawa-Goto K, Tokuda H, Iida A, Suzuki N, Qian K, Lee KH. A-ring modified betulinic acid derivatives as potent cancer preventive agents. Bioorg Med Chem Lett 2014; 24: 1005-1008
- 24 Hung HY, Nakagawa-Goto K, Tokuda H, Iida A, Suzuki N, Morris-Natschke SL, Lee KH. Cancer preventive agents 11. Novel analogs of dimethyl dicarboxylate biphenyl as potent cancer chemopreventive agents. Pharm Biol 2012; 50: 18-24
- 25 Suzuki M, Nakagawa-Goto K, Nakamura S, Tokuda H, Morris-Natschke SL, Kozuka M, Nishino H, Lee KH. Cancer preventive agents. Antitumor-promoting effects of coumarins and related compounds on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis. Pharm Biol 2006; 44: 178-182
- 26 Wang X, Nakagawa-Goto K, Kozuka M, Tokuda H, Nishino H, Lee KH. Cancer preventive agents. Part 6: Chemopreventive potential of furanocoumarins and related compounds. Pharm Biol 2006; 44: 116-120
- 27 Nakagawa-Goto K, Oda A, Hamel E, Ohkoshi E, Lee KH, Goto M. Development of a novel class of tubulin inhibitor from desmosdumotin B with a hydroxylated bicyclic B-ring. J Med Chem 2015; 58: 2378-2389