title: Isolation and structure elucidation of parnafungins C and D, isoxazolidinone-containing antifungal natural products.
abstract: Parnafungins, natural products containing an isoxazolidinone ring, have been isolated from Fusarium larvarum and have been shown to be potent inhibitors of the fungal polyadenosine polymerase. The extraction and analysis of fermentation broths of taxonomically related organisms identified as closely related Fusarium spp. produce not only parnafungin A and B, but also significant quantities of two related components. These members of the paranfungin family of natural products have been isolated and the structure of each has been elucidated. While structurally analogous to parnafungin A, parnafungin C is further elaborated by methylation of a phenolic hydroxyl group, and parnafungin D has both the methyl phenol ether as well as an epoxide in the xanthone ring system. Parnafungin C and D have potent, broad spectrum antifungal activity and also have been shown to target fungal mRNA cleavage and polyadenylation.
authors.affiliation: Centro de Investigación Básica, Merck, Sharp & Dohme de España, S. A., Josefa Valcárcel, Madrid E-28027, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Overy
authors.forename: Kathleen
authors.initials: K
authors.lastname: Calati
authors.forename: Jennifer Nielsen
authors.initials: JN
authors.lastname: Kahn
authors.forename: Ming-Jo
authors.initials: MJ
authors.lastname: Hsu
authors.forename: Jesús
authors.initials: J
authors.lastname: Martín
authors.forename: Javier
authors.initials: J
authors.lastname: Collado
authors.forename: Terry
authors.initials: T
authors.lastname: Roemer
authors.forename: Guy
authors.initials: G
authors.lastname: Harris
authors.forename: Craig A
authors.initials: CA
authors.lastname: Parish
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D005670:Fusarium / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D023303:Oxazolidinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D001688:Biological Products; D023303:Oxazolidinones; C538877:parnafungin C; C538878:parnafungin D