Synthesis and anti-tumor activity of carbohydrate analogues of the tetrahydrofuran containing acetogenins.

Abstract

The tetrahydrofuran (THF) containing annonaceous acetogenins (AAs) are attractive candidates for drug development because of their potent cytotoxicity against a wide range of tumors and their relatively simple and robust structures. Replacement of the THF segment with a sugar residue may deliver analogues with improved tumor selectivity and pharmacokinetics and are therefore attractive for drug development. As a first test to the feasibility of such structures, a set of such monosaccharide analogues was synthesized and assayed against four human tumor cell lines, cervical (HeLa), breast (MDA-MB231), T-cell leukemia (Jurkat) and prostate (PC-3). Certain analogues showed low micromolar activity that was comparable to a structurally similar, naturally occurring mono-THF acetogenin. A preliminary examination of the structure-activity profile of these carbohydrate analogues suggests that they have a similar mechanism of action as their THF congeners.

• Authors: Stewart Bachan, K A Tony, Akira Kawamura, Diego Montenegro, Anjali Joshi, Himanshu Garg, David R Mootoo
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 21 Issue 21 Pg. 6554-64 (Nov 01 2013) ISSN: 1464-3391 [Electronic] England
• PMID: 24045006 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Acetogenins
• Antineoplastic Agents
• Carbohydrates
• Furans
• tetrahydrofuran

Topics

• Acetogenins (chemical synthesis, chemistry, toxicity)
• Antineoplastic Agents (chemical synthesis, chemistry, toxicity)
• Carbohydrates (chemistry)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Furans (chemistry)
• HeLa Cells
• Humans
• Jurkat Cells
• Light
• Scattering, Radiation
• Stereoisomerism
• Structure-Activity Relationship