title: Iodinated Meroditerpenes from a Red Alga Callophycus sp.
abstract: Unique iodine-containing meroditerpenes iodocallophycoic acid A (1) and iodocallophycols A-D (2-5) were discovered from the Fijian red alga Callophycus sp. Because flexibility of the molecular skeleton impaired full characterization of relative stereochemistries by NMR spectroscopy, a DFT-based theoretical model was developed to derive relevant interproton distances which were compared to those calculated from NOE measurements, yielding the relative stereochemistries. The correct 2S,6S,7S,10S,14S enantiomers were then identified by comparison of theoretical and experimental ECD spectra. Biological activities of these iodinated and brominated meroditerpenes and additional new, related bromophycoic acid F (6) and bromophycoic acid A methyl ester (7), were evaluated for relevant human disease targets. Iodocallophycoic acid A (1) showed moderate antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) with MIC values of 1.4 and 2.2 μg mL-1, respectively. It also potentiated the anti-MRSA activity of oxacillin in a synergistic fashion, resulting in an 8-fold increase in oxacillin potency, for a MIC of 16 μg mL-1.
authors.affiliation: School of Chemistry and Biochemistry and ‡School of Biological Sciences, Aquatic Chemical Ecology Center, Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.|Department of Dermatology, ⊥Center for the Study of Human Health, and ∥Antibiotic Resistance Center, Emory University , Atlanta, Georgia 30322, United States.
authors.forename: Serge
authors.identifier: 0000-0002-7792-9737
authors.initials: S
authors.lastname: Lavoie
authors.affiliation: School of Chemistry and Biochemistry and ‡School of Biological Sciences, Aquatic Chemical Ecology Center, Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.|Department of Dermatology, ⊥Center for the Study of Human Health, and ∥Antibiotic Resistance Center, Emory University , Atlanta, Georgia 30322, United States.
authors.forename: David
authors.initials: D
authors.lastname: Brumley
authors.affiliation: School of Chemistry and Biochemistry and ‡School of Biological Sciences, Aquatic Chemical Ecology Center, Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.|Department of Dermatology, ⊥Center for the Study of Human Health, and ∥Antibiotic Resistance Center, Emory University , Atlanta, Georgia 30322, United States.
authors.forename: Troy S
authors.initials: TS
authors.lastname: Alexander
authors.affiliation: School of Chemistry and Biochemistry and ‡School of Biological Sciences, Aquatic Chemical Ecology Center, Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.|Department of Dermatology, ⊥Center for the Study of Human Health, and ∥Antibiotic Resistance Center, Emory University , Atlanta, Georgia 30322, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Jasmin
authors.affiliation: School of Chemistry and Biochemistry and ‡School of Biological Sciences, Aquatic Chemical Ecology Center, Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.|Department of Dermatology, ⊥Center for the Study of Human Health, and ∥Antibiotic Resistance Center, Emory University , Atlanta, Georgia 30322, United States.
authors.forename: Franz A
authors.initials: FA
authors.lastname: Carranza
authors.affiliation: School of Chemistry and Biochemistry and ‡School of Biological Sciences, Aquatic Chemical Ecology Center, Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.|Department of Dermatology, ⊥Center for the Study of Human Health, and ∥Antibiotic Resistance Center, Emory University , Atlanta, Georgia 30322, United States.
authors.forename: Kate
authors.initials: K
authors.lastname: Nelson
authors.affiliation: School of Chemistry and Biochemistry and ‡School of Biological Sciences, Aquatic Chemical Ecology Center, Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.|Department of Dermatology, ⊥Center for the Study of Human Health, and ∥Antibiotic Resistance Center, Emory University , Atlanta, Georgia 30322, United States.
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Quave
authors.affiliation: School of Chemistry and Biochemistry and ‡School of Biological Sciences, Aquatic Chemical Ecology Center, Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.|Department of Dermatology, ⊥Center for the Study of Human Health, and ∥Antibiotic Resistance Center, Emory University , Atlanta, Georgia 30322, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Kubanek
mesh_terms: D004224:Diterpenes / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D016984:Enterococcus faecium / Q000187:drug effects; D007455:Iodine / Q000737:chemistry*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical; D000461:Rhodophyta / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods; D013237:Stereoisomerism
chemical_list: D004224:Diterpenes; D007455:Iodine