| Abstract
| - Two ether glucosyl diglyceride analogs were synthesized, and theirantiproliferative activityagainst four epithelial cancer cell lines was evaluated.1-O-Hexadecyl-2-O-methyl-3-O-(2‘-acetamido-2‘-deoxy-β-d-glucopyranosyl)-sn-glycerol(4) was synthesized by reaction of 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-d-glucopyranosylchloride with1-O-hexadecyl-2-O-methyl-sn-glycerol followed by deacetylation by methanolichydrolysis. The N-acetyl group of 4wasremoved by hydrolysis with ethanolic potassium hydroxide to form1-O-hexadecyl-2-O-methyl-3-O-(2‘-amino-2‘-deoxy-β-d-glucopyranosyl)-sn-glycerol(5). Compounds 4 and 5 inhibitedtheproliferation of MCF-7, A549, A427, and T84 cancer cell lines. TheIC50 values for 5 rangedfrom 6.5 to 12.2 μM, whereas 4 was more effective againstA549 cells (IC50 9 μM) than againstMCF-7 (IC50 17 μM) and A427 (IC50 25 μM)cells and was inactive against T84 cells. Underidentical incubation conditions, compounds 4 and5 were potent inhibitors of the proliferationof OVCAR-3 cells with IC50 values of 12 and 4 μM,respectively, whereas ET-18-OCH3,hexadecylphosphocholine, and erucylphosphocholine had IC50values of 24, >30, and >30 μM,respectively. The cell-inhibitory profile of these ether-linkedglucosyl diglycerides strengthensthe hypothesis that such glycolipids represent a distinct group ofantitumor ether lipids, havingantineoplastic activities that differ from the well-knownalkylphosphocholines and alkyllysophospholipids.
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