Synthesis and Evaluation of the Antiproliferative Effects of 1-O-Hexadecyl-2-O- methyl-3-O-(2‘-acetamido-2‘-deoxy-β-d-glucopyranosyl)-sn-glycerol and 1-O-Hexadecyl-2-O-methyl-3-O-(2‘-amino-2‘-deoxy-β-d-glucopyranosyl)-sn-glycerol on Epithelial Cancer Cell Growth

• Published in: Journal of medicinal chemistry Vol. 39; no. 7; pp. 1545 - 1548
• Main Authors: Erukulla, Ravi Kumar, Zhou, Xi, Samadder, Pranati, Arthur, Gilbert, Bittman, Robert
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 29.03.1996; Amer Chemical Soc
• Subjects: Antineoplastic agents; Biological and medical sciences; Chemistry, Medicinal; General aspects; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Adenocarcinoma; Antineoplastic agent; Carcinoma; Ether; Diglyceride; Cytotoxicity; Malignant tumor; In vitro; Biological activity; Glycolipid; Aminoglycoside; Established cell line; Chemical synthesis; Tumor cell
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm950928f

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-β-d-glucopyranosyl)-sn-glycerol (4) was synthesized by reaction of 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-α-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-β-d-glucopyranosyl)-sn-glycerol (5). Compounds 4 and 5 inhibited the proliferation of MCF-7, A549, A427, and T84 cancer cell lines. The IC50 values for 5 ranged from 6.5 to 12.2 μM, whereas 4 was more effective against A549 cells (IC50 9 μM) than against MCF-7 (IC50 17 μM) and A427 (IC50 25 μM) 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 IC50 values of 12 and 4 μM, respectively, whereas ET-18-OCH3, hexadecylphosphocholine, and erucylphosphocholine had IC50 values of 24, >30, and >30 μM, 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.