Synthesis and evaluation of the antiproliferative effects of 1-O-hexadecyl-2-O-methyl-3-O-(2'-acetamido-2'-deoxy-beta-D- glucopyranosyl)-sn-glycerol and 1-O-hexadecyl-2-O-methyl-3-0- (2'-amino-2'-deoxy-beta-D-glucopyranosyl)-sn-glycerol on epithelial cancer cell growth.
Two ether glucosyl diglyceride analogs were synthesized, and their antiproliferative activity against four epithelial cancer cell lines was evaluated. 1-O-Hexadecyl-2-O-methyl-3-O-(2'-acetamido-2'-deoxy-beta-D- glucopyranosyl)-sn-glycerol (4) was synthesized by reaction of 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-alpha-D-glucopyranosyl chloride with 1-O-hexadecyl-2-O-methyl-sn-glycerol followed by deacetylation by methanolic hydrolysis. The N-acetyl group of 4 was removed by hydrolysis with ethanolic potassium hydroxide to form 1-O-hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-beta-D-glucopyranosyl)- sn-glycerol (5). Compounds 4 and 5 inhibited the proliferation of MCF-7, A549, A427, and T84 cancer cell lines. The IC(50) values for 5 ranged from 6.5 to 12.2 microM, whereas 4 was more effective against A549 cells (IC(50) 9 microM) than against MCF-7 (IC(50) 17 microM) and A427 (IC(50) 25 microM) cells and was inactive against T84 cells. Under identical incubation conditions, compounds 4 and 5 were potent inhibitors of the proliferation of OVCAR-3 cells with IC(50) values of 12 and 4 microM, respectively, whereas ET-18-OCH(3), hexadecylphosphocholine, and erucylphosphocholine had IC(50) values of 24, >30, and >30 microM, respectively. The cell-inhibitory profile of these ether-linked glucosyl diglycerides strengthens the hypothesis that such glycolipids represent a distinct group of antitumor ether lipids, having antineoplastic activities that differ from the well-known alkylphosphocholines and alkyllysophospholipids.
Erukulla
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RK
Department of Chemistry and Biochemistry, Queens College of the City University of New York, Flushing, New York 11367-1597, USA.
Zhou
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Samadder
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Arthur
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Bittman
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D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D004075:Diglycerides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006017:Glycolipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000473:pathology*; D014407:Tumor Cells, Cultured
C100469:1-O-hexadecyl-2-O-methyl--3-O-methyl-(2'-amino-2'-deoxyglucopyranosyl)-sn-glycerol; C100468:1-O-hexadecyl-2-O-methyl-3-O-(2'-acetamido-2'-deoxyglucopyranosyl)-sn-glycerol; D000970:Antineoplastic Agents; D004075:Diglycerides; D006017:Glycolipids