Celebesides A−C and Theopapuamides B−D, Depsipeptides from an Indonesian Sponge That Inhibit HIV-1 Entry
2008; American Chemical Society; Volume: 74; Issue: 2 Linguagem: Inglês
10.1021/jo802232u
ISSN1520-6904
AutoresAlberto Plaza, Giuseppe Bifulco, Jessica L. Keffer, John R. Lloyd, Heather L. Baker, Carole A. Bewley,
Tópico(s)Carbohydrate Chemistry and Synthesis
ResumoSix new depsipeptides belonging to two different structural classes, termed celebesides A−C and theopapuamides B−D, have been isolated from the marine sponge Siliquariaspongia mirabilis. Their structures were determined using extensive 2D NMR and ESI-MS/MS techniques. Celebesides are unusual cyclic depsipeptides that comprise a polyketide moiety and five amino acid residues, including an uncommon 3-carbamoyl threonine, and a phosphoserine residue in celebesides A and B. Theopapuamides B−D are undecapeptides with an N-terminal fatty acid moiety containing two previously unreported amino acids, 3-acetamido-2-aminopropanoic acid and 4-amino-2,3-dihydroxy-5-methylhexanoic acid. The relative configuration of the polyketide moiety in celebesides was resolved by J-based analysis and quantum mechanical calculations, the results of which were self-consistent. Celebeside A neutralized HIV-1 in a single-round infectivity assay with an IC50 value of 1.9 ± 0.4 μg/mL while the nonphosphorylated analog celebeside C was inactive at concentrations as high as 50 μg/mL. Theopapuamides A−C showed cytotoxicity against human colon carcinoma (HCT-116) cells with IC50 values between 2.1 and 4.0 μg/mL and exhibited strong antifungal activity against wildtype and amphotericin B-resistant strains of Candida albicans at loads of 1−5 μg/disk.
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