Synthesis and pharmacological activity evaluation of 2-(2-Phenylethyl)chromone analogues: The principal components in agarwood.

2-(2-Phenylethyl)chromones (PECs), the pivotal constituents responsible for the distinctive aroma and pharmacological potential of agarwood, are primarily obtained through extraction from natural materials. The restricted availability of agarwood has, however, hindered a comprehensive and systematic evaluation of their biological properties. In this study, we have chemically synthesized a total of 38 PEC derivatives, including 23 new compounds that had not been previously isolated from agarwood. These compounds were then evaluated for their inhibitory effects on nitric oxide release, neutrophil superoxide production, as well as their activities against tyrosinase, acetylcholinesterase, and α-glucosidase. The preliminary screening resulted in the identification of promising leads with potential therapeutic activities, and the structure-activity relationship of the synthesized PECs have also been briefly discussed. The results provide a foundation for the synthesis and pharmacological exploration of PECs, which sheds light on the pharmacological potential of agarwood's secondary metabolites.