Resin Glycosides from Ipomoea funis as Inhibitors of P-Glycoprotein in Multidrug-Resistant Breast Carcinoma Cells.

Ipomoea funis Cham. & Schltdl. is an endemic vine found in central Mexico. The use of heart-cutting and peak-shaving methods in recycling preparative HPLC yielded funisin I (1), an undescribed resin glycoside, along with the known intrapilosins I (2) and V (3). Funisin I features operculinic acid A (6) as the oligosaccharide core. The structural similarities observed for funisin I align with those previously reported for purginoside I (4); however, a difference was apparent in the occurrence of dodecanoic and (-)-(2R)-methylbutyric acids as the long- and short-chain fatty acid substituents in compound 1. Moreover, the structure of the previously described acutacoside F (5) was corrected by comparing its NMR data with those of 1 and 4. The three isolated glycolipids (1-3) did not show intrinsic cytotoxicity. However, intrapilosin I (2), when combined (50 μM) with a sublethal concentration of the antineoplastic drug vinblastine at 0.004 μM, significantly improved its cytotoxic effect and ability to reverse the vinblastine-resistant phenotype in MCF-7 cells by arresting the cell cycle at the G2/M phase and acting as a competitive substrate for P-gp. Resin glycosides could become promising alternatives for developing new therapeutic combinatory strategies to combat multidrug resistance in cancer treatment.