title: 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.affiliation: Department of Chemistry, Hunter College, 695 Park Avenue, New York, NY 10065, USA.
authors.forename: Stewart
authors.initials: S
authors.lastname: Bachan
authors.forename: K A
authors.initials: KA
authors.lastname: Tony
authors.forename: Akira
authors.initials: A
authors.lastname: Kawamura
authors.forename: Diego
authors.initials: D
authors.lastname: Montenegro
authors.forename: Anjali
authors.initials: A
authors.lastname: Joshi
authors.forename: Himanshu
authors.initials: H
authors.lastname: Garg
authors.forename: David R
authors.initials: DR
authors.lastname: Mootoo
mesh_terms: D054378:Acetogenins / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002241:Carbohydrates / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005663:Furans / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008027:Light; D012542:Scattering, Radiation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D054378:Acetogenins; D000970:Antineoplastic Agents; D002241:Carbohydrates; D005663:Furans; C018674:tetrahydrofuran
keywords: Carbohydrate; Dynamic light scattering; Lipid; Metathesis; Mimetic
references.citation: Nat Prod Rep. 2005 Apr;22(2):269-303
references.pmid: 15806200
references.citation: Phytochemistry. 1996 May;42(2):253-71
references.pmid: 8688168
references.citation: Carbohydr Res. 2008 Oct 13;343(15):2680-6
references.pmid: 18760404
references.citation: J Am Chem Soc. 2003 Sep 17;125(37):11360-70
references.pmid: 16220959
references.citation: Nat Prod Rep. 1996 Aug;13(4):275-306
references.pmid: 8760865
references.citation: J Nat Prod. 2008 Jul;71(7):1311-21
references.pmid: 18598079
references.citation: J Photochem Photobiol B. 1990 Nov;7(2-4):359-61
references.pmid: 2128330
references.citation: Angew Chem Int Ed Engl. 2003 Apr 29;42(17):1900-23
references.pmid: 12730969
references.citation: Bioorg Med Chem. 2008 Sep 15;16(18):8413-8
references.pmid: 18774299
references.citation: Cancer Metastasis Rev. 2001;20(3-4):245-77
references.pmid: 12085965
references.citation: J Nat Prod. 1996 Feb;59(2):97-9
references.pmid: 8991957
references.citation: Curr Drug Targets. 2003 Jan;4(1):23-30
references.pmid: 12528987
references.citation: Biochim Biophys Acta. 1998 Jul 20;1365(3):443-52
references.pmid: 9711297
references.citation: Carbohydr Res. 2005 Oct 17;340(14):2245-50
references.pmid: 16084504
references.citation: J Med Chem. 2000 Apr 20;43(8):1604-10
references.pmid: 10780917
references.citation: Int J Endocrinol. 2010;2010:
references.pmid: 20706540
references.citation: J Nat Prod. 1999 Mar;62(3):504-40
references.pmid: 10096871
references.citation: Planta Med. 2010 Sep;76(13):1390-404
references.pmid: 20577943
references.citation: J Nat Prod. 1989 May-Jun;52(3):463-77
references.pmid: 2778448
references.citation: Chem Pharm Bull (Tokyo). 1998 Jan;46(1):154-8
references.pmid: 9468648
references.citation: Molecules. 2009 Sep 17;14(9):3621-61
references.pmid: 19783948
references.citation: J Am Chem Soc. 2005 Jul 27;127(29):10396-9
references.pmid: 16028952