4′-O-Alkyaloenin derivatives and their sulfates directed toward overcoming multidrug resistance in tumor cells

The cytotoxic effects on HCT 116, Hep G2 and HCT 116/VCR 100-1-1 cell lines of synthetic 4′-O-alkylaloenins (2–17), 4′-O-benzylaloenin (18) and 4′-O-allylaloenin (19) were examined by MTT assay, and compared with that of aloenin (1) isolated from Aloe arborescens Mill. Var. natalensis Berger which showed no marked effect (IC50 value: >100 μM). The cytotoxic effects of 4′-O-alkylaloenin sulfates (21–29) were also examined on the same cell lines. The introduction of a longer alkyl group at the O-4′ position of 1 resulted in a higher cytotoxic action on HCT 116 and Hep G2 cells. Among 4′-O-alkylaloenins 2–17, 4′-O-tetradecylaloenin 14 was the most cytotoxic to both on HCT 116 cells (IC50 value: 5.3±2.3 μM) and Hep G2 cells (IC50 value: 4.0±0.6 μM). Also among 4′-O-alkylaloenin sulfates 21–29, 4′-O-dodecylaloenin sulfate 29 was the most cytotoxic to both on HCT 116 (IC50 value: 4.8±0.2 μM) and Hep G2 cells (IC50 value: 4.0±0.5 μM). 4′-O-Alkylaloenins 7–14 and 4′-O-alkylaloenin sulfates 24–29 were also cytotoxic to Hep G2 and HCT 116/VCR 100-1-1 cell lines, which overexpress P-glycoprotein, as well as HCT 116 cell lines which scarcely express it.