2-(2-Phenylethyl)chromone Derivatives in Chinese Agarwood “Qi-Nan” from Aquilaria sinensis

Abstract

Five new 2-(2-phenylethyl)chromone derivatives, qinanones A−E (1–5), together with eight known 2-(2-phenylethyl)chromone derivatives (6–13), were isolated from the Et₂O extract of high-quality Chinese agarwood “Qi-Nan” originating from Aquilaria sinensis. The structures of the new 2-(2-phenylethyl)chromones were elucidated by spectroscopic techniques (UV, IR, 1D and 2D NMR) and MS analyses. In the bioassay for acetylcholinesterase inhibitors, compounds 1–6, 10, and 12 exhibited weak inhibitory activities (inhibition percentage ranged from 10 % to 24 % at the concentration of 50 µg/mL). Compared with other agarwoods, “Qi-Nan” was different in containing 2-(2-phenylethyl)chromones with unsubstituted chromone rings.

Key words

Aquilaria sinensis - Thymelaeaceae - Qi-Nan - 2-(2-phenylethyl)chromone derivatives - AChE inhibitory activities

• References

• 1 Ng LT, Chang YS, Kadir AA. A review on agar (gaharu) producing Aquilaria species. J Trop For Prod 1997; 2: 272-285
• 2 Ito M. Studies on perilla, agarwood, and cinnamon through a combination of fieldwork and laboratory work. J Nat Med 2008; 62: 387-395
• 3 Persoon GA, Beek HH. Smallholder tree growing for rural development and environmental services, Volume 5. Amsterdam: Springer Netherlands; 2008: 245-262
• 4 Barden A, Anak NA, Mulliken T, Song M. Heart of the matter: agarwood use and trade and CITES implementation for Aquilaria malaccensis . Cambridge: TRAFFIC International; 2000: 1-51
• 5 Borris RP, Blaskó G, Cordell GA. Ethnopharmacologic and phytochemical studies of the Thymelaeaceae. J Ethnopharmacol 1988; 24: 41-91
• 6 Jia TM. Xiang Xue Qi Jiang. Beijing: Writers Publishing House; 2010: 7
• 7 China Pharmacopoeia Editorial Board. Pharmacopoeia of the Peopleʼs Republic of China. Beijing: China Medical Science and Technology Press; 2010: 172
• 8 Naef R. The volatile and semi-volatile constituents of agarwood, the infected heartwood of Aquilaria species: a review. Flav Fragr J 2011; 26: 73-87
• 9 Chen HQ, Wei JH, Yang JS, Zhang Z, Yang Y, Gao ZH, Sui C, Gong B. Chemical constituents of agarwood originating from the endemic genus Aquilaria plants. Chem Biodivers 2012; 9: 236-250
• 10 Alkhathlan HZ, Al-Hazimi HM, Al-Dhalaan FS, Mousa AA. Three 2-(2-phenylethyl)chromones and two terpenes from agarwood. Nat Prod Res 2005; 19: 367-372
• 11 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
• 12 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
• 13 Wu B, Lee JG, Lim CJ, Jia SD, Kwon SW, Hwang GS, Park JH. Sesquiterpenoids and 2-(2-phenylethyl)-4H-chromen-4-one (= 2-(2-Phenylethyl)-4H-1-benzopyran-4-one) derivatives from Aquilaria malaccensis agarwood. Helv Chim Acta 2012; 95: 636-642
• 14 Yang L, Qiao LR, Xie D, Yuan YH, Chen NH, Dai JG, Guo SX. 2-(2-Phenylethyl)chromones from Chinese eaglewood. Phytochemistry 2012; 76: 92-97
• 15 Chen D, Xu ZR, Chai XY, Zeng KW, Jia YX, Bi D, Ma ZZ, Tu PF. 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
• 16 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
• 17 Ishihara M, Tsuneya T, Uneyama K. Components of the agarwood smoke on heating. J Essent Oil Res 1993; 5: 419-423
• 18 Lim TW, Noorainie AA. Wood for trees: a review of the agarwood (gaharu) trade in Malaysia. Petaling Jaya, Selangot: TRAFFIC Southeast Asia; 2010: 1-65
• 19 Qi SY, He ML, Lin LD, Zhang CH, Hu LJ, Zhang HZ. Production of 2-(2-phenylethyl)chromones in cell suspension cultures of Aquilaria sinensis . Plant Cell Tissue Organ Cult 2005; 83: 217-221
• 20 Ito M, Okimoto KI, Yagura T, Honda G, Kiuchi F, Shimada Y. Induction of sesquiterpenoid production by methyl jasmonate in Aquilaria sinensis cell suspension culture. J Essent Oil Res 2005; 17: 175-180
• 21 Okudera Y, Ito M. Production of agarwood fragrant constituents in Aquilaria calli and cell suspension cultures. Plant Biotechnol 2009; 26: 307-315
• 22 Kenmotsu Y, Yamamura Y, Ogita S, Katoh Y, Kurosaki F. Transcriptional activation of putative calmodulin genes Am-cam-1 and Am-cam-2 from Aquilaria microcarpa, in response to external stimuli. Biol Pharm Bull 2010; 33: 1911-1914
• 23 Kumeta Y, Ito M. Characterization of δ-guaiene synthases from cultured cells of Aquilaria, responsible for the formation of the sesquiterpenes in agarwood. Plant Physiol 2010; 154: 1998-2007
• 24 Kenmotsu Y, Ogita S, Katoh Y, Yamamura Y, Takao Y, Tatsuo Y, Fujino H, Kadota S, Kurosaki F. Methyl jasmonate-induced enhancement of expression activity of Am-FaPS-1, a putative farnesyl diphosphate synthase gene from Aquilaria microcarpa . J Nat Med 2011; 65: 194-197
• 25 Zhang XL, Liu YY, Wei JH, Yang Y, Zhang Z, Huang JQ, Chen HQ, Liu YJ. Production of high-quality agarwood in Aquilaria sinensis trees via whole-tree agarwood-induction technology. Chin Chem Lett 2012; 23: 727-730
• 26 Wooten JR, Filip To SD, Igathinathane C, Pordesimo LO. Discrimination of bark from wood chips through texture analysis by image processing. Comput Electronics Agric 2011; 79: 13-19
• 27 Yazid K, Masschaele B, Awang MRB, Abdullah MZ, Saleh JM, Mohamed AA, Khalid MABH. Three-dimensional imaging using microcomputed tomography for studying gaharu morphology. AIP Conference Proceedings 2010; 1202: 127-130
• 28 Najib MS, Taib MN, Ali NAM, Arip MNM, Jalil AM. Classification of agarwood grades using ANN. Classification of agarwood grades using ANN. International Conference on Electrical, Control and Computer Engineering (INECCE), Kuantan. 2011
• 29 Hidayat W, Shakaff AYM, Ahmad MN, Adom AH. Classification of agarwood oil using an electronic nose. Sensors 2010; 10: 4675-4685
• 30 Wetwitayaklung P, Thavanapong N, Charoenteeraboon J. Chemical constituents and antimicrobial activity of essential oil and extracts of heartwood of Aquilaria crassna obtained from water distillation and supercritical fluid carbon dioxide extraction. Silpakorn Univ Sci Technol J 2009; 3: 25-33
• 31 Ibrahim AH, Al-Rawi SS, Majid AMSA, Rahman NNA, Salah KMA, Kadir MOAP. Separation and fractionation of Aquilaria malaccensis oil using supercritical fluid extraction and the cytotoxic properties of the extracted oil. Proc Food Sci 2011; 1: 1953-1959
• 32 Pornpunyapat J, Chetpattananondh P, Tongurai C. Mathematical modeling for extraction of essential oil from Aquilaria crassna by hydrodistillation and quality of agarwood oil. Bangladesh J Pharmacol 2011; 6: 18-24
• 33 Yamagata E, Yoneda K. Pharmacognostical studies on the crude drug of agarwood (VI): on “Kanankoh”. Shoyakugaku Zasshi 1987; 41: 142-146
• 34 Nakanishi T, Inada A, Nishi M, Yamagata E, Yoneda K. A new and a known derivatives of 2-(2-phenylethyl)chromone from a kind of agarwood (“Kanankoh,” in Japanese) originating from Aquilaria agallocha . J Nat Prod 1986; 49: 1106-1108
• 35 Barden A, Anak NA, Mulliken T, Song M. Heart of the matter: agarwood use and trade and CITES implementation for Aquilaria malaccensis . Cambridge: TRAFFIC International; 2000: 7
• 36 Ishihara M, Tsuneya T, Shiga M, Uneyama K. Three sesquiterpenes from agarwood. Phytochemistry 1991; 30: 563-566
• 37 Ishihara M, Tsuneya T, Uneyama K. Guaiane sesquiterpenes from agarwood. Phytochemistry 1991; 30: 3343-3347
• 38 Ishihara M, Tsuneya T, Uneyama K. Fragrant sesquiterpenes from agarwood. Phytochemistry 1993; 33: 1147-1155
• 39 Ueda JY, Imamura L, Tezuka Y, Tran QL, Tsuda M, Kadota S. New sesquiterpene from Vietnamese agarwood and its induction effect on brain-derived neurotrophic factor mRNA expression in vitro . Bioorg Med Chem 2006; 14: 3571-3574
• 40 Okugawa H, Ueda R, Matsumoto K, Kawanishi K, Kato A. Effect of jinkoh-eremol and agarospirol from agarwood on the central nervous system in mice. Planta Med 1996; 62: 2-6
• 41 Okugawa H, Ueda R, Matsumoto K, Kawanishi K, Kato K. Effects of sesquiterpenoids from “Oriental incenses” on acetic acid-induced writhing and D₂ and 5-HT_2A receptors in rat brain. Phytomedicine 2000; 7: 417-422
• 42 Okugawa H, Ueda R, Matsumoto K, Kawanishi K, Kato A. Effects of agarwood extracts on the central nervous system in mice. Planta Med 1993; 59: 32-36
• 43 Takemoto H, Ito M, Shiraki T, Yagura T, Honda G. Sedative effects of vapor inhalation of agarwood oil and spikenard extract and identification of their active components. J Nat Med 2008; 62: 41-46
• 44 Yoon JS, Lee MK, Sung SH, Kim YC. Neuroprotective 2-(2-phenylethyl)chromones of Imperata cylindrica . J Nat Prod 2006; 69: 290-291
• 45 Choi PJ, Rathwell DCK, Brimble MA. Synthesis of 6,6-bisbenzannulated spiroketals related to the rubromycins using a double intramolecular hetero-Michael addition (DIHMA). Tetrahedron Lett 2009; 50: 3245-3248
• 46 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
• 47 Yang JS, Wang YL, Su YL. Studies on the chemical constituents of Aquilaria sinensis (Lour.) Gilg. IV. Isolation and characterization of 2-(2-phenylethyl)chromone derivatives. Acta Pharm Sin 1989; 24: 678-683
• 48 Konishi T, Konoshima T, Shimada Y, Kiyosawa S. Six new 2-(2-phenylethyl)chromones from agarwood. Chem Pharm Bull 2002; 50: 419-422
• 49 Liu JM, Gao YH, Xu HH, Xu ZQ. Chemical constituents of Lignum Aquilariae Resinatum (II). Chin Tradit Herb Drugs 2007; 38: 1138-1140
• 50 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
• 51 Ellman GL, Courtney KD, Valentino AJ, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7: 88-95