Reinvestigation of the CHCl(3)-soluble extract from aerial parts of Ipomoea purga was carried out to identify mammalian multidrug-resistance inhibitors. Preparative-scale recycling HPLC was used to purify four new resin
glycosides, purgins II (1) and III (2) in addition to purginosides III (3) and IV (4), as well as the known purginosides I (5) and II (6) and
purgin I (7). The structures of 1-4 were established through NMR spectroscopy and mass spectrometry. Purgins II (1) and III (2) are the first examples of
ester-type dimers of
operculinic acid B with three different acylating residues in both monomeric units: (2S)-methylbutyric
acid, n-hexanoic, n-decanoic, and trans-cinnamic
acids. The macrolactonization site was located at C-2 of the second saccharide unit. The position of the
ester linkage for monomeric unit B on the macrocyclic unit A was established as C-4 of the terminal
glucose. Purginosides III (3) and IV (4) were found to be pentasaccharides of
operculinic acid A with a structure related to that previously described for compounds 5 and 6. Reversal of multidrug resistance by compounds 1-7 was evaluated in
vinblastine-resistant human
breast carcinoma cells (MCF-7/Vin).
Purgin II (1) enhanced
vinblastine activity >2140-fold when incorporated at 25 μg/mL. For compounds 2-7, a moderate
vinblastine-enhancing activity from 1.4-fold to 6.5-fold was observed.