PTP1B inhibitory and cytotoxic activities of triterpenoids from the aerial parts of Agrimonia pilosa

Recently, PTP1B inhibitors have become the frontier as possible targeting for anti-cancer and anti-diabetic drugs. Twelve triterpenoids from the aerial parts of Agrimonia pilosa were investigated for PTP1B inhibitory and cytotoxic activities. In the results, compounds 3 (IC50 = 0.50 μM) and 7 (IC50 = 5.88 μM) were found to possess very powerful inhibitory activity against the PTP1B enzyme, comparable to the positive control ursolic acid (IC50 = 6.60 μM). In addition, compounds 1, 2, 4, and 10‒12 showed potent inhibitory effects against PTP1B, with an IC50 range of 13.48‒14.98 μM. In the kinetic assay of the PTP1B enzyme, compounds 1 and 2 were noncompetitive, whereas 7 and 11 showed a mixed type. In the docking analysis, the results showed that different residues of PTP1B interacted with twelve triterpenoids. Furthermore, compounds 6 (IC50 = 3.65 μM) and 12 (IC50 = 1.21 μM) displayed strong cytotoxic effects against the HeLa cell line. Compounds 2 (IC50 = 16.06 μM) and 4 (IC50 = 14.73 μM) showed moderate cytotoxic activities against the HeLa cell line. Compound 2 exhibited comprehensive cytotoxicity against the HL-60 (IC50 = 45.53 μM) and MCF-7 (IC50 = 34.21 μM) cell lines. These results support the use of triterpenoids in traditional medicine for prevention and treatment of diabetes and cancer.