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 IC(50) value of 1.9 +/- 0.4 microg/mL while the nonphosphorylated analog celebeside C was inactive at concentrations as high as 50 microg/mL. Theopapuamides A-C showed cytotoxicity against human colon carcinoma (HCT-116) cells with IC(50) values between 2.1 and 4.0 microg/mL and exhibited strong antifungal activity against wildtype and amphotericin B-resistant strains of Candida albicans at loads of 1-5 microg/disk.
Plaza
Alberto
A
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0820, USA.
Bifulco
Giuseppe
G
Keffer
Jessica L
JL
Lloyd
John R
JR
Baker
Heather L
HL
Bewley
Carole A
CA
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011161:Porifera / Q000737:chemistry*; D011789:Quantum Theory; D021241:Spectrometry, Mass, Electrospray Ionization; D053586:Virus Internalization / Q000187:drug effects*
D000970:Antineoplastic Agents; D047630:Depsipeptides; C538733:celebeside A; C538732:celebeside B; C516618:theopapuamide