Resin Glycosides from <i>Ipomoea funis</i> as Inhibitors of P-Glycoprotein in Multidrug-Resistant Breast Carcinoma Cells

<i>Ipomoea funis</i> 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 (<b>1</b>), an undescribed resin glycoside, along with the known intrapilosins I (<b>2</b>) and V (<b>3</b>). Funisin I features operculinic acid A (<b>6</b>) as the oligosaccharide core. The structural similarities observed for funisin I align with those previously reported for purginoside I (<b>4</b>); however, a difference was apparent in the occurrence of dodecanoic and (-)-(2<i>R</i>)-methylbutyric acids as the long- and short-chain fatty acid substituents in compound <b>1</b>. Moreover, the structure of the previously described acutacoside F (<b>5</b>) was corrected by comparing its NMR data with those of <b>1</b> and <b>4</b>. The three isolated glycolipids (<b>1</b>-<b>3</b>) did not show intrinsic cytotoxicity. However, intrapilosin I (<b>2</b>), 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.