Pentasaccharide resin glycosides with multidrug resistance reversal activities from the seeds of Pharbitis nil

Abstract

Resin glycosides are novel P-glycoprotein inhibitors. In order to evaluate their multidrug resistance (MDR) reversal activities, we isolated seven new resin glycosides, pharbitins A–G (1–7) from the seeds of Pharbitis nil. Their chemical structures were determined by extensive application of high resolution 2D NMR techniques, HRESIMS and chemical methods. Compounds 1–4 and 6 were evaluated for their MDR reversal activities in KB/VCR, A549/T and K562/ADR cells. Among them, compound 2 showed moderate MDR reversal activity in KB/VCR cells, and increased the cytotoxicity of vincristine by 2.2-fold when incorporated at 25 μM. A structure–activity relationship study revealed that substituting Rha′′ C-3 with a trans-cinnamoyl group improves the MDR reversal activity. Also, an intracellular Rh123 accumulation assay demonstrated that compound 2 could inhibit the function of P-gp.