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Synthesis and growth inhibitory properties of glycosides of 1-O-hexadecyl-2-O-methyl-sn-glycerol, analogs of the antitumor ether lipid ET-18-OCH3 (edelfosine).
J Med Chem. 1996 Aug 16; 39(17):3241-7.JM

Abstract

Glycosylated antitumor ether lipids (GAELs), analogs of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (1, ET-18-OCH3, edelfosine), were synthesized in good overall yields by glycosylation of 1-O-alkyl-2-O-methyl-sn-glycerol and tested for in vitro antineoplastic activity against a variety of murine and human tumor cell lines. Stereospecific glycosylation was achieved by the use of 2-O-acetyl-3,4,6-tri-O-benzylglucopyranosyl and -mannopyranosyl trichloroacetimidates as donors, with trimethylsilyl trifluoromethanesulfonate as catalyst in the presence of molecular sieves at -78 degrees C. The GAELs differ from 1 in having the sn-3-phosphocholine residue replaced by one of the following monosaccharide residues: beta- and alpha-2-deoxy-D-arabino-hexopyranosyl, alpha-D-mannopyranosyl, 2-O-methyl-beta-D-glucopyranosyl, and 2-O-methyl-alpha-D-mannopyranosyl. 1-O-Hexadecyl-2-O-methyl-3-O-(2'-deoxy-beta-D-arabino-hexopyranosyl)- sn-glycerol (2) was more effective than 1 in inhibiting the growth of MCF-7 (human breast cancer) and its adriamycin-resistant form MCF-7/adriamycin, and murine Lewis lung cancer cells. 2-Deoxy-beta-D-arabino-hexopyranoside 2 was also an effective growth inhibitor of two drug-resistant leukemic cell lines, P388/Adr and L1210/vmdr.

Authors+Show Affiliations

Department of Chemistry and Biochemistry, Queens College of the City University of New York, Flushing, New York 11367-1597, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8765506

Citation

Marino-Albernas, J R., et al. "Synthesis and Growth Inhibitory Properties of Glycosides of 1-O-hexadecyl-2-O-methyl-sn-glycerol, Analogs of the Antitumor Ether Lipid ET-18-OCH3 (edelfosine)." Journal of Medicinal Chemistry, vol. 39, no. 17, 1996, pp. 3241-7.
Marino-Albernas JR, Bittman R, Peters A, et al. Synthesis and growth inhibitory properties of glycosides of 1-O-hexadecyl-2-O-methyl-sn-glycerol, analogs of the antitumor ether lipid ET-18-OCH3 (edelfosine). J Med Chem. 1996;39(17):3241-7.
Marino-Albernas, J. R., Bittman, R., Peters, A., & Mayhew, E. (1996). Synthesis and growth inhibitory properties of glycosides of 1-O-hexadecyl-2-O-methyl-sn-glycerol, analogs of the antitumor ether lipid ET-18-OCH3 (edelfosine). Journal of Medicinal Chemistry, 39(17), 3241-7.
Marino-Albernas JR, et al. Synthesis and Growth Inhibitory Properties of Glycosides of 1-O-hexadecyl-2-O-methyl-sn-glycerol, Analogs of the Antitumor Ether Lipid ET-18-OCH3 (edelfosine). J Med Chem. 1996 Aug 16;39(17):3241-7. PubMed PMID: 8765506.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and growth inhibitory properties of glycosides of 1-O-hexadecyl-2-O-methyl-sn-glycerol, analogs of the antitumor ether lipid ET-18-OCH3 (edelfosine). AU - Marino-Albernas,J R, AU - Bittman,R, AU - Peters,A, AU - Mayhew,E, PY - 1996/8/16/pubmed PY - 1996/8/16/medline PY - 1996/8/16/entrez SP - 3241 EP - 7 JF - Journal of medicinal chemistry JO - J Med Chem VL - 39 IS - 17 N2 - Glycosylated antitumor ether lipids (GAELs), analogs of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (1, ET-18-OCH3, edelfosine), were synthesized in good overall yields by glycosylation of 1-O-alkyl-2-O-methyl-sn-glycerol and tested for in vitro antineoplastic activity against a variety of murine and human tumor cell lines. Stereospecific glycosylation was achieved by the use of 2-O-acetyl-3,4,6-tri-O-benzylglucopyranosyl and -mannopyranosyl trichloroacetimidates as donors, with trimethylsilyl trifluoromethanesulfonate as catalyst in the presence of molecular sieves at -78 degrees C. The GAELs differ from 1 in having the sn-3-phosphocholine residue replaced by one of the following monosaccharide residues: beta- and alpha-2-deoxy-D-arabino-hexopyranosyl, alpha-D-mannopyranosyl, 2-O-methyl-beta-D-glucopyranosyl, and 2-O-methyl-alpha-D-mannopyranosyl. 1-O-Hexadecyl-2-O-methyl-3-O-(2'-deoxy-beta-D-arabino-hexopyranosyl)- sn-glycerol (2) was more effective than 1 in inhibiting the growth of MCF-7 (human breast cancer) and its adriamycin-resistant form MCF-7/adriamycin, and murine Lewis lung cancer cells. 2-Deoxy-beta-D-arabino-hexopyranoside 2 was also an effective growth inhibitor of two drug-resistant leukemic cell lines, P388/Adr and L1210/vmdr. SN - 0022-2623 UR - https://www.unboundmedicine.com/medline/citation/8765506/Synthesis_and_growth_inhibitory_properties_of_glycosides_of_1_O_hexadecyl_2_O_methyl_sn_glycerol_analogs_of_the_antitumor_ether_lipid_ET_18_OCH3__edelfosine__ L2 - https://doi.org/10.1021/jm960164j DB - PRIME DP - Unbound Medicine ER -