Isolation of limonoids and alkaloids from Phellodendron amurense and their multidrug resistance (MDR) reversal activity.
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), 12alpha-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 microg/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 microg/mL and 0.0011 microg/mL, respectively.
Min
Yong Deuk
YD
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
Kwon
Hak Cheol
HC
Yang
Min Cheol
MC
Lee
Kyu Ha
KH
Choi
Sang Un
SU
Lee
Kang Ro
KR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D036701:Limonins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D032102:Phellodendron / Q000737:chemistry; D024301:Plant Bark; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D036701:Limonins