title: Structural correlates of antifungal and cytotoxic activity of brefeldin A: the importance of a rigid planar lactone ring.
abstract: Molecular modelling of brefeldin A and its derivatives shows that the presence of a rigid and planar lactone ring conformation is necessary for cytotoxic and anti-fungal activity. Cytotoxic compounds had lactone ring torsion angles of -28.77 +/- 6.13 degrees, while non-cytotoxic compounds had torsion angles of -88.25 +/- 14.6 degrees.
authors.affiliation: Department of Microbiology, University of Reading, Whiteknights, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Crabbe
authors.forename: V
authors.initials: V
authors.lastname: Betina
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D020126:Brefeldin A; D016923:Cell Death / Q000187:drug effects; D003517:Cyclopentanes / Q000737:chemistry* / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D003517:Cyclopentanes; D020126:Brefeldin A