title: Studies on n-octyl-5-(alpha-D-arabinofuranosyl)-beta-D-galactofuranosides for mycobacterial glycosyltransferase activity.
abstract: The mycobacterial cell wall is a potential target for new drug development. Herein we report the preparation and activity of several n-octyl-5-(alpha-D-arabinofuranosyl)-beta-D-galactofuranoside derivatives. A cell-free assay system has been utilized for determination of the ability of disaccharide analogues to act as arabinosyltransferase acceptors using [14C]-DPA as the glycosyl donor. In addition, in vitro inhibitory activity has been determined in a colorimetric broth microdilution assay system against MTB H37Ra and three clinical isolates of Mycobacterium avium complex (MAC). One of these disaccharides showed moderate activity against MTB. The biological evaluation of these disaccharides suggests that more hydrophobic analogues with a blocked reducing end showed better activity as compared to a totally deprotected disaccharide that more closely resembles the natural substrates in cell wall biosynthesis.
authors.affiliation: Department of Organic Chemistry, Southern Research Institute, PO Box 55305, Birmingham, AL 35255, USA.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Pathak
authors.forename: Vibha
authors.initials: V
authors.lastname: Pathak
authors.forename: William J
authors.initials: WJ
authors.lastname: Suling
authors.forename: Sudagar S
authors.initials: SS
authors.lastname: Gurcha
authors.forename: Caroline B
authors.initials: CB
authors.lastname: Morehouse
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Maddry
authors.forename: Robert C
authors.initials: RC
authors.lastname: Reynolds
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016695:Glycosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000187:drug effects / Q000201:enzymology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: D000995:Antitubercular Agents; D004187:Disaccharides; D004791:Enzyme Inhibitors; D011135:Polysaccharides, Bacterial; D016695:Glycosyltransferases; D010430:Pentosyltransferases; C101967:arabinosyltransferase