Isolation of limonoids and alkaloids from Phellodendron amurense and their multidrug resistance (MDR) reversal activity

Abstract

Three limonoids and five alkaloids were isolated from the chloroform layer of the MeOH extract of the bark of Phellodendron amurense (Rutaceae). The structures of the compounds isolated were determined to be obacunone (1), limonin (2), 12 alpha-hydroxylimonin (3), gamma-fagarine (4), oxyberberine (5), canthin-6-one (6), 4-methoxy-N-methyl-2-quinolone (7) and oxypalmatine (8) based on the physicochemical and spectroscopic data. Compounds 3, 5, 7, and 8 were first isolated from the Phellodendron amurense. The isolated compounds were then tested for their cytotoxicity against five human tumor cell lines in vitro using the SRB method. Compound 5 showed significant cytotoxicity against the five tumor cell lines with ED50 values ranging from 0.30 to 3.0 mu g/mL. The marginal or noncytotoxic compounds (1, 2, 3, 4, and 7) were examined for their P-gp related MDR reversal activities. Compound 1 showed significant P-gp MDR inhibition activity in MES-SA/DX5 and HCT15 cells with an ED50 value of 0.028 mu g/mL and 0.0011 mu g/mL, respectively.