Celebesides A-C and Theopapuamides B-D, Depsipeptides from an Indonesian Sponge That Inhibit HIV-1 Entry

Six 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 mu g/mL while the nonphosphorylated analog celebeside C was inactive at concentrations as high as 50 mu g/mL. Theopapuamides A-C showed cytotoxicity against human colon carcinoma (HCT-116) cells with IC50 values between 2.1 and 4.0 mu g/mL and exhibited strong antifungal activity against wildtype and amphotericin B-resistant strains of Candida albicans at loads of 1-5 mu g/disk.