Four New 2-(2-Phenylethyl)-4H-chromen-4-one Derivatives from the Resinous Wood of Aquilaria sinensis and Their Inhibitory Activities on Neutrophil Pro-Inflammatory Responses

Abstract

Four new 2-(2-phenylethyl)-4-chromen-4-one derivatives, 6-hydroxy-5-methoxy-2-[2-(4'-methoxyphenyl)ethyl]chromone (1: ), 6,7-dimethoxy-2-[2-(2'-hydroxyphenyl)ethyl]chromone (2: ), 5-hydroxy-6-methoxy-2-[2-(3'-methoxyphenyl)ethyl]-chromone (3: ), and 7-chloro-8-hydroxy-2-[2-(4'-methoxyphenyl)ethyl]chromone (4: ), have been isolated from the resinous wood of , together with 16 known compounds (5: -20: ). Among these, 7-methoxy-2-[2-(4'-methoxyphenyl)ethyl]chromone (5: ) was isolated from a natural source for the first time. The structures of the new compounds were established by spectroscopic analyses (1D and 2D NMR, HR-ESI-MS, IR, UV). Nine compounds, including 1: showed more than 80% inhibition of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine at 50 µM.

Chemical and Bioactivity Diversity of 2‐(2‐Phenylethyl)chromones in Agarwood: A Review

“…Several FTPECs (compounds 130 , 104 , 124 , and 74 ) show excellent anti‐inflammatory activities. Moreover, at 50 μM, they inhibited greater than 80 % of the N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine‐indued superoxide anion production in human neutrophils [39] . Chen reported that the IC 50 values of compounds 119 , 109 , 76 , 121 , and 98 are in the range of 5.12–22.26 μM, which indicates significant inhibition of NO production in RAW 264.7 cells [38] .…”

“…Moreover, at 50 μM, they inhibited greater than 80 % of the N-formyl-L-methionyl-Lleucyl-L-phenylalanine-indued superoxide anion production in human neutrophils. [39] Chen reported that the IC 50 values of compounds 119, 109, 76, 121, and 98 are in the range of 5.12 -22.26 μM, which indicates significant inhibition of NO production in RAW 264.7 cells. [38] Moreover, we discovered that the 8-hydroxy group enhances the activities of compounds 77 (IC 50 .…”

“…THPECs exhibited anti‐inflammatory, [7,8,38–40] AChE inhibitory, [41–44] cytotoxic [45–47] and phosphodiesterase (PDE) 3A inhibitory activities [48] . Compounds 41 and 42 , which are THPECs, exhibit AChE inhibitory activities at a concentration of 50 μg/mL [10] .…”

“…The anti‐inflammatory, [7,38–51] AChE inhibitory, [10,42,47,48,52–55] antioxidant, [9,17] cytotoxic, [6,10,54,56,57] PPARγ partial agonist, [58] tyrosinase inhibitory, [59] neuroprotective, [5,60] α ‐glucosidase inhibitory, [61,62] and antibacterial activities [10,6,54,63] of various FHPECs.…”

“…EPECs exhibit anti-inflammatory, [7,39,67] AChE inhibitory, [10,12,41,68] antibacterial, [10] and cytotoxic activities. [12,41,55] Notably, the movement of B cells is inhibited by GYF-21 (compound 174), mainly via blockage of the BAFF-stimulated signaling pathways.…”