title: Isolation, structure elucidation, and antibacterial activity of methiosetin, a tetramic acid from a tropical sooty mold (Capnodium sp.).
abstract: Drug-resistant bacteria continue to make many existing antibiotic classes ineffective. In order to avoid a future epidemic from drug-resistant bacterial infections, new antibiotics with new modes of action are needed. In an antibiotic screening program for new drug leads with new modes of action using antisense Staphylococcus aureus Fitness Test screening, we discovered a new tetramic acid, methiosetin, from a tropical sooty mold, Capnodium sp. The fungus also produced epicorazine A, a known antibiotic. The structure and relative configuration of methiosetin was elucidated by 2D NMR and ESIMS techniques. Methiosetin and epicorazine A showed weak to modest antibacterial activity against S. aureus and Haemophilus influenzae. The isolation, structure elucidation, and antibacterial activity of both compounds are described.
authors.affiliation: Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey 07065, United States.
authors.forename: Kithsiri
authors.initials: K
authors.lastname: Herath
authors.forename: Hiranthi
authors.initials: H
authors.lastname: Jayasuriya
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Zink
authors.forename: Jan
authors.initials: J
authors.lastname: Sigmund
authors.forename: Francisca
authors.initials: F
authors.lastname: Vicente
authors.forename: Mercedes
authors.initials: M
authors.lastname: de la Cruz
authors.forename: Angela
authors.initials: A
authors.lastname: Basilio
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Bills
authors.forename: Jon D
authors.initials: JD
authors.lastname: Polishook
authors.forename: Robert
authors.initials: R
authors.lastname: Donald
authors.forename: John
authors.initials: J
authors.lastname: Phillips
authors.forename: Michael
authors.initials: M
authors.lastname: Goetz
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001203:Ascomycota / Q000737:chemistry*; D006166:Guatemala; D006193:Haemophilus influenzae / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010879:Piperazines / Q000302:isolation & purification / Q000494:pharmacology; D011760:Pyrrolidinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D010879:Piperazines; D011760:Pyrrolidinones; C572037:methiosetin; C009435:tetramic acid; C018283:epicorazine A