A chlorinated 2-(2-phenylethyl)chromone in artificial agarwood as a DRD5 agonist and mediates the cAMP/Ca²⁺ signaling pathway to intervene in the growth and proliferation of gastric cancer cells

A chlorinated 2-(2-phenylethyl)chromone from artificial agarwood of Aquilaria sinensis was identified as a dopamine receptor D5 (DRD5) agonist. Comprehensive analyses the protein–protein interaction network, molecular docking, ADMET prediction, and molecular dynamics simulation revealed strong DRD5 binding and modulation of the cAMP/Ca²⁺ pathway in gastric cancer. The compound exhibited potent cytotoxic activity against MGC-803 and SGC-7901 cells in vitro. ADMET profiling revealed favorable pharmacokinetics and a promising safety profile. Compound CHE emerges as a promising lead therapeutic candidate for gastric cancer derived from agarwood. • The novel chlorinated chromone compound CHE is identified for the first time as a dopamine receptor D5 (DRD5) agonist. • Compound CHE inhibits gastric cancer cell proliferation and targets treatment through the cAMP/Ca 2 + pathway. • Compound CHE possesses excellent pharmacokinetic properties.