LC-HRMS Metabolite Profiling of Lunasia amara Stem Bark and In Silico Study in Breast Cancer Receptors

L. amara is a medicinal plant used as an aphrodisiac. Several studies show it has a compound with biological activities such as inhibition of cell proliferation, one of the mechanisms leading to anticancer activities. This study aimed to profile the metabolites and predict activity against two breast cancer receptors (ERα (3ERT) and HER2 (3PPO)) with an in silico approach. Metabolite profiling of water and 80% ethanol extract was analyzed by UHPLC-Q-Orbitrap-HRMS. Also, we performed a radical scavenging activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH). Putative identification of metabolite in L. amara showed the 46 metabolites (4 unknown) were identified and predominantly as quinoline alkaloids. Some of the compounds from glycosides and phenol groups were also identified. From the antioxidant capacity test results, the 80% ethanol extract had a higher radical scavenging capacity than the aqueous extract. Based on the molecular docking results, the highest affinity for the ERα receptor was found in the tested compound tetrahydropapaveroline and exceeded the native 4-OHT ligand. For the HER2 receptor, graveolinine has the highest affinity but is still below the native lapatinib ligand. Ligand interactions with the amino acids Leu 387 and Glu 419 on the active site of the ERα receptor and Phe1004 on the HER2 receptor are thought to play an important role in increasing the energy affinity. Overall, all compounds showed higher affinity for HER2 receptors than ERα. Alkaloids demonstrated anticancer activity. Further research should be conducted to determine the in vitro activity of these compounds on breast cancer cells.