Sesquiterpenoids and 2-(2-phenylethyl)chromones respectively acting as α-glucosidase and tyrosinase inhibitors from agarwood of an Aquilaria plant

Abstract

The ethyl ether extract of agarwood from an Aquilaria plant afforded six new sesquiterpenoids, Agarozizanol A − F ( 1 − 6 ), together with four known sesquiterpenoids and six known 2-(2-phenylethyl)chromones. Their structures were elucidated via detailed spectroscopic analysis, X-ray diffraction, and comparisons with the published data. All the isolates were evaluated for the α-glucosidase and tyrosinase inhibitory activities in vitro . Compounds 5 , 7 , 8 , and 10 showed significant inhibition of α-glucosidase with IC 50 values ranging between 112.3 ± 4.5 and 524.5 ± 2.7 µM (acarbose, 743. 4 ± 3.3 µM). Compounds 13 and 14 exhibited tyrosinase inhibitory effect with IC 50 values of 89.0 ± 1.7 and 51.5 ± 0.6 µM, respectively (kojic acid, 46.1 ± 1.3). In the kinetic studies, compounds 5 and 14 were found to be uncompetitive inhibitors for α-glucosidase and mixed type inhibitors for tyrosinase, respectively. Furthermore, molecular docking simulations revealed the binding sites and interactions of the most active compounds with α-glucosidase and tyrosinase.

Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

“…Finally, moderate-high activity has been very recently reported for phenylethylchromones isolated from the agarwood of Aquilaria plants [120,121] and anthraquinones from Cassia tora seeds [122] (Figure 16). Interestingly, polyamine derivatives comprising coumaroyl and caffeoyl moieties from bee pollen of Quercus mongolica have been also described as tyrosinase inhibitors [119].…”

“…Finally, moderate-high activity has been very recently reported for phenylethylchromones isolated from the agarwood of Aquilaria plants [120,121] and anthraquinones from Cassia tora seeds [122] ( Figure 16).…”

Concise Total Synthesis of Agarozizanol B via a Strained Photocascade Intermediate

“…The enantiomeric (−)‐form of 1 and (−)‐prezizanol ( 3 ) were found in the oil of Eremophila georgei , a flowering plant of the figwort family [4, 5] . More recently, di‐ and trioxygenated sesquiterpenes with a prezizane skeleton (agarozizanols, [6] aquilarenes [7] ) were isolated from agarwood and arose some interest due to their activity as α‐glucosidase inhibitors.…”

“…Cleavage of the indicated bond [16] would allow for immediate formation of the skeleton with all 15 carbon atoms already present in the key intermediate. We now report the successful implementation of this strategy which allowed us to access agarozizanol B ( 4 ) [6] both in racemic and in enantiopure form. The absolute configuration of its naturally occurring (+)‐enantiomer (+)‐ 4 could be established.…”

Pharmacokinetic studies of six major 2‐(2‐phenylethyl) chromones in rat plasma using ultra high performance liquid chromatography with tandem mass spectrometry after oral administration of agarwood ethanol extract

“…AH 1 has also been chosen as the testing standard and used to evaluate the quality of agarwood in the Chinese Pharmacopoeia (Chp) due to its high content and good stability [4,19]. Furthermore, 8-CHL reportedly exhibits weak inhibitory effects on tyrosinase [20] and has significant anti-inflammatory effects [21]. AH 6 has been shown to inhibit acetylcholinesterse [22] and could inhibit LPS-stimulated NF-kB activation with relative luciferase activity in RAW264.7 macrophages [23].…”