Agarwood knowledge

Agarwood is the resinous heartwood from Aquilaria or Gyrinops species (Thymelaeaceae), which also called eaglewood, gaharu, jinko, aloeswood, kanankoh, kyara, jinkoh, chenxiang or oud in different cultures [1,2]. Aquilaria crassna Pierre ex Lecomte, one of the important resources of agarwood in the world market, mainly grow in Laos, Thailand, Cambodia and Vietnam [3].

2-(2-Phenylethyl)chromone, an important type of characteristic component in agarwood, which was also the main class of active ingredient of agarwood [1,2,4]. So far, >150 2-(2-phenylethyl)chromone derivatives have been identified from agarwood of some Aquilaria species [[4], [5], [6], [7], [8]], while, vast majority of these 2-(2-phenylethyl)chromones were monomers, not polymers. Since Japanese researchers acquired a few 2-(2-phenylethyl)chromone polymers from agarwood in Kalimantan in the 1980s [[9], [10], [11], [12]], there haven't been identified any new 2-(2-phenylethyl)chromone polymer from agarwood until 2017. From the year 2017 to now, 30 new dimeric 2-(2-phenylethyl)chromones have been identified from agarwood of Aquilaria sinensis and Aquilaria crassna respectively [[5], [6], [7], [8]], which could be a breakthrough on the phytochemical study of agarwood. Due to the great separation potential of chromone polymer from agarwood, further studies on this type of compounds could be performed seriously in the future.

As an indispensable part of our study on bioactive chemical constituents of agarwood from A. crassna, previous investigation on agarwood of A. crassna from Laos, led to the isolation of a series of 2-(2-phenylethyl)chromone derivatives [5,6,13,14] and some eremophilane sesquiterpenes [[13], [14], [15]]. During our ongoing research for bioactive 2-(2-phenylethyl)chromone derivatives, four dimeric chromones (1–4) were obtained from agarwood of A. crassna. All dimeric chromones were evaluated for their cytotoxic activity against three human cancer cell lines in vitro. Compounds 1 and 3 showed weak cytotoxicity against human hepatocellular carcinoma BEL-7402 cell line with IC50 values of 44.68 and 42.10 μΜ. This paper described the structural elucidation of the four new dimeric 2-(2-phenylethyl)chromones (1–4), as well as their cytotoxic activities.

Agarwood is the fragrant resinous heartwood harvested from the Aquilaria species of the family Thymelaeaceae, which was mostly distributed in China, Japan, India and Southeast Asian countries [1], [2] and was widely used in incenses, perfumes, traditional medicines and other products in the world market [3]. Aquilaria sinensis (Lour.) is the main plant resource of Chinese agarwood, and the wild agarwood was close to exhausted due to the condition particularity of formation and a long period of time required for agar to accumulate in the wound tissues of trees [4], [5], coupled with the increase of commercial demand resulted in the anthropogenic deforestation. Fortunately, the holing method has widely been accepted recently to produce artificial agarwood attributed to the good quality of the product and the lasting aroma of its ether extract [5], [6]. Despite the commercial and biological significance of artificial agarwood, only a few researches on chemical constituents was conducted, which led to a series of sesquiterpenoids and 2-(2-phenylethyl)chromones [7], [8], [9], [10], [11].

Though 2-(2-phenylethyl)chromones were widely distributed in agarwood, and was considered as one of diagnostic components of agarwood quality [8], [9], [12], [13], the research progress about phenylethylchromone polymers (including dimer and trimer) was slow that no more than eleven analogues have been reported since the first one was isolated from the Kalimantan agalwood named “Jinko” and characterized by Iwagoe et al. in 1986 [14], [15], [16], [17], [18].

With the aim to study the chemical constituent of artificial agarwood, as well as to expand the diversity of bioactivities and chemical structures of bi-phenylethylchromones, the ongoing chemical investigation on agarwood induced by artificial holing was carried out, which led to the isolation and identification of four new bi-phenylethylchromone derivatives (1–4). Their structures were elucidated by extensive UV, IR, 1D and 2D NMR, and the absolute configuration was determined by electronic circular dichroism (ECD) spectroscopic analysis. All compounds were tested for AChE and α-glucosidase inhibitory activity.

Agarwood is the resinous heartwood containing fragrant resin obtained from the trees of Aquilaria and Gyrinops species after they get physical injury or microbial attack [1,2]. To date, twenty-one species in the genus Aquilaria and nine species in the genus Gyrinops have been documented scattered extensively in south China, Myanmar, Thailand, Vietnam, India, and other Southeast Asia countries [2,3]. Aquilaria walla is recorded mainly distributing in the wet and intermediate zones of Sri Lanka, and minority in southwest India [4]. Its agarwood appears usually black with small white spots and has unique cool fragrance [5].

Modern phytochemistry studies indicated that 2-(2-phenylethyl)chromones are one of the main characteristic components in agarwood exhibiting various of biological activities [[6], [7], [8], [9], [10]]. Previous chemical studies on A. walla have led to identify three new 2-(2-phenylethyl)chromones, especially including an unprecedented flavonoid-2-(2-phenylethyl)chromone, which displayed significant cytotoxicity versus five human cancer cell lines [5,[11], [12], [13]]. In order to look for more interesting structures from agarwood of A. walla, the continuing research was carried out, and two rare flavonoid-2-(2-phenylethyl)chromones (1,2) and five new dimeric 2-(2-phenylethyl)chromones (3–7) were further isolated. In vitro cytotoxic assessment using MTT method showed that compound 1 presented cytotoxic activity versus the same five human cancer cell lines with IC50 values ranging from 13.40 to 28.96 μM.