Isolation and bioactivity evaluation of the chemical constituents from Bridelia balansae Tutcher

Abstract

From our in vitro high throughput screening study of around 3000 plant extracts, the dichloromethane fraction of the roots of Bridelia balansae Tutcher (Phyllanthaceae) showed potential anticancer activity, with an IC50 value at 0.8 µg/mL against HCT116 colon cancer cell. B. balansae has been used as a folk medicine to treat cataclasis and traumatic injury in China. There is no prior report of the bioactivity of the chemical constituents from B. balansae. To identify the potential anticancer lead molecules, the plant materials of B. balansae were recollected and extracted with methanol. Bioassay-directed fractionation of the extract led to the isolation of 16 compounds. Among them, four (1 – 4) showed cancer cell killing activity against HCT116 cell line with the IC50 values at 20 nM, 33.5, 20.0 and 16.3µM, respectively (Table 1). Compounds 1 and 5 are new ones. Compound 1, an α-peltatin, demonstrated the most significant cytotoxic activity among all the isolates. It was evaluated against a panel of cancer cell lines (A375, HCT116, HT29 and A549) and showed highest cytotoxicity against HCT116 and the melanoma A375 cell lines, with the IC50 values at 20 nM and 7 nM, respectively. Compound 1 is a retro-lactone analogue of podophylotoxin (the carbonyl carbon located at C-11 in 1 but at C-12 in podophylotoxin). In our study, compound 1 showed much higher cancer cell killing activity than etoposide (an FDA approved anticancer drug) in two cell lines (HCT116 and A375) (Table 1). Previous study [1] showed that etoposide has much higher activity than the 4-hydroxyl analogue (6) of compound 1, indicating the presence of the hydroxyl group at C-4 significantly reduced cancer cell killing activity for a retro-podophylotoxin compound. The in vitro cancer cell killing potency of this retro-podophylotoxin compound provides basements for further structure-activity relationship (SAR) and in vivo studies.