title: Synthesis of new analogs of echinocandin B by enzymatic deacylation and chemical reacylation of the echinocandin B peptide: synthesis of the antifungal agent cilofungin (LY121019).
abstract: The antifungal antibiotic, echinocandin B (ECB), was modified by a sequential procedure in which the initial step involved enzymatic removal of the native N-linoleoyl group from the N-terminus using an Actinoplanes utahensis culture. The resulting product, ECB nucleus, was reacylated using active esters or acid halides of various substituted acids to give a series of ECB analogs. These analogs possessed anti-Candida activity both in vitro and in vivo (mice). Other studies have shown that one of these, cilofungin, the 4-n-octyloxybenzoyl-ECB analog (LY121019), has excellent anti-Candida activity, low toxicity and is superior to other available antifungal antibiotics.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
authors.forename: M
authors.initials: M
authors.lastname: Debono
authors.forename: B J
authors.initials: BJ
authors.lastname: Abbott
authors.forename: D S
authors.initials: DS
authors.lastname: Fukuda
authors.forename: M
authors.initials: M
authors.lastname: Barnhart
authors.forename: K E
authors.initials: KE
authors.lastname: Willard
authors.forename: R M
authors.initials: RM
authors.lastname: Molloy
authors.forename: K H
authors.initials: KH
authors.lastname: Michel
authors.forename: J R
authors.initials: JR
authors.lastname: Turner
authors.forename: T F
authors.initials: TF
authors.lastname: Butler
authors.forename: A H
authors.initials: AH
authors.lastname: Hunt
mesh_terms: D000215:Acylation; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents / Q000138:chemical synthesis*; D054714:Echinocandins; D005656:Fungal Proteins; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010456:Peptides, Cyclic; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D010455:Peptides; D010456:Peptides, Cyclic; C042101:cilofungin; C007572:echinocandin B