title: New PKS-NRPS tetramic acids and pyridinone from an Australian marine-derived fungus, Chaunopycnis sp.
abstract: Chemical analysis of a marine-derived fungus, Chaunopycnis sp. (CMB-MF028), isolated from the inner tissue of a pulmonate false limpet Siphonaria sp., collected from rock surfaces in the intertidal zone of Moora Park, Shorncliffe, Queensland, yielded the tetramic acid F-14329 (1) and new analogues, chaunolidines A-C (2-4), together with the new pyridinone chaunolidone A (5), and pyridoxatin (6). Structures inclusive of absolute configurations were assigned to 1-6 on the basis of detailed spectroscopic analysis, X-ray crystallography, electronic circular dichroism (ECD), biosynthetic considerations and chemical interconversion. Chaunolidine C (4) exhibits modest Gram-positive antibacterial activity (IC50 5-10 μM), while chaunolidone A (5) is a selective and potent inhibitor (IC50 0.09 μM) of human non-small cell lung carcinoma cells (NCI-H460). Tetramic acids 1-4 form metal chelates with Fe(III), Al(III), Cu(II), Mg(II) and Zn(II).
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia. r.capon@uq.edu.au.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Shang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Breno P
authors.initials: BP
authors.lastname: Espósito
authors.forename: Angela A
authors.initials: AA
authors.lastname: Salim
authors.forename: Zeinab G
authors.initials: ZG
authors.lastname: Khalil
authors.forename: Michelle
authors.initials: M
authors.lastname: Quezada
authors.forename: Paul V
authors.initials: PV
authors.lastname: Bernhardt
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Capon
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry / Q000187:drug effects* / Q000302:isolation & purification; D001315:Australia; D001419:Bacteria / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D049851:Gastropoda / Q000469:parasitology; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011728:Pyridones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D011728:Pyridones; D011760:Pyrrolidinones; C009435:tetramic acid