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Three new anabaenopeptin-like peptides, named paltolides A-C, were isolated from a deep-water specimen of the marine sponge Theonella swinhoei from Palau. Paltolides belong to a rare subgroup of sponge-derived anabaenopeptins that have in common a C-terminal tryptophan residue linked to the epsilon-amine of a lysine bearing a d configuration. The structures of paltolides A-C were determined by NMR and tandem MS techniques. Paltolide A is the first anabaenopeptin structure where a non-N-methylated amino acid precedes the C-terminal residue.

A new highly unsaturated macrolide lactam, termed mirabilin ( 1), was isolated from the aqueous extract of the marine sponge Siliquariaspongia mirabilis. Mirabilin is characterized by the presence of a 35-membered macrolide lactam ring bearing a pentadiene conjugated system and a tetrasubstituted tetrahydropyran ring. A linear polyketide moiety is attached to the macrocyclic ring through an amide linkage. The structure of mirabilin was determined using extensive 2D NMR and ESIMS and tandem MS techniques. Mirabilin inhibits the growth of the tumor cell line HCT-116 with an IC 50 value of 0.27 +/- 0.09 microM and is noncytotoxic to several other cell lines.

Seven new chromone-containing polyketides, termed cystochromones A-G, were isolated from the myxobacterial strain Cystobacter sp. MCy9104. Their structures were elucidated using comprehensive NMR spectroscopy and HR-MS/MS. Cystochromones bear a pentadecyl moiety unusually attached at C-5 of the chromone ring. Moreover, isotope-labeled substrate feeding experiments and NMR analysis suggested a hybrid iso-fatty acid and polyketide synthase biosynthetic pathway for these secondary metabolites.

Five new 14,15-secopregnane derivatives, named argelosides K-O (1-5), have been isolated from Solenostemma argel leaves. Their structures were established by a detailed spectroscopic analysis. In particular, argeloside N (1) showed in the sugar portion an unusual 3-O-methyl-2,6-dideoxyhexopyranose unit characterized by the occurrence of a Delta3 double bond, and argeloside O (5) displayed an unusual moiety linked to position 3 probably derived by the oxidation of a 3-O-methyl-2,6-dideoxyhexopyranose unit. The propensity of compounds 2, 3, and 5 and argeloside F (6) to inhibit TNF-alpha release by LPS-stimulated RAW 264.7 mouse cells was evaluated.

Two new dammarane saponins identified as jujubogenin 3-O-alpha-l-arabinofuranosyl(1-->2)-[beta-d-glucopyranosyl(1-->6) beta-d-glucopyranosyl(1-->3)]-alpha-l-arabinopyranoside (2) and jujubogenin 3-O-alpha-l-arabinofuranosyl(1-->2)-[6-O-[3-hydroxy-3-methylglutaryl]-beta-d-glucopyranosyl(1-->3)]-alpha-l-arabinopyranoside (3) and a new lupane saponin, 3beta-hydroxylup-20(29)-en-27,28-dioic acid 28-O-beta-d-glucopyranosyl(1-->2)-[beta-d-xylopyranosyl(1-->3)]-beta-d-xylopyranosyl(1-->2)-beta-d-glucopyranoside ester (5), along with the known jujubogenin 3-O-alpha-l-arabinofuranosyl(1-->2)-[beta-d-glucopyranosyl(1-->3)]-alpha-l-arabinopyranoside (1) and 3beta-hydroxylup-20(29)-ene-27,28-dioic acid (4), were isolated from the methanol extract of the stems of Anomospermum grandifolium. The structures of the new compounds were established by spectral analysis. Antimicrobial activity screening of compounds 1-3 revealed antifungal properties against C. albicans ATCC 3153 for compounds 2 and 3. The antibacterial and antifungal activities of the petroleum ether, chloroform, and methanol extracts of A. grandifolium stems were also evaluated.

The 18 kb "silent" luminmycin biosynthetic pathway from Photorhabdus luminescens was cloned into a vector by using the newly established linear-linear homologous recombination and successfully expressed in Escherichia coli. Luminmycins A-C (1-3) were isolated from the heterologous host, and their structures were elucidated using 2D NMR spectroscopy and HRESIMS. Luminmycin A is a deoxy derivative of the previously reported glidobactin A, while luminmycins B and C most likely represent its acyclic biosynthetic intermediates. Compound 1 showed cytotoxicity against the human colon carcinoma HCT-116 cell line with an IC(50) value of 91.8 nM, while acyclic 2 was inactive at concentrations as high as 100 μg/mL.

A new highly unsaturated macrolide lactam, termed mirabilin ( 1), was isolated from the aqueous extract of the marine sponge Siliquariaspongia mirabilis. Mirabilin is characterized by the presence of a 35-membered macrolide lactam ring bearing a pentadiene conjugated system and a tetrasubstituted tetrahydropyran ring. A linear polyketide moiety is attached to the macrocyclic ring through an amide linkage. The structure of mirabilin was determined using extensive 2D NMR and ESIMS and tandem MS techniques. Mirabilin inhibits the growth of the tumor cell line HCT-116 with an IC 50 value of 0.27 +/- 0.09 microM and is noncytotoxic to several other cell lines.

Four new cyclic depsipeptides termed mirabamides A-D (1-4) have been isolated from the marine sponge Siliquariaspongia mirabilis and shown to potently inhibit HIV-1 fusion. Their structures were elucidated by NMR and ESIMS, and absolute stereochemistry of the amino acids was determined using advanced Marfey's methods and NMR. Mirabamides contain two new entities, including 4-chlorohomoproline in 1-3 and an unusual glycosylated amino acid, beta-methoxytyrosine 4'-O-alpha-L-rhamnopyranoside (in 1, 2, and 4), along with a rare N-terminal aliphatic hydroxy acid. These elements proved to be useful for anti-HIV structure-activity relationship studies. Mirabamide A inhibited HIV-1 in neutralization and fusion assays with IC50 values between 40 and 140 nM, as did mirabamides C and D (IC50 values between 140 nM and 1.3 microM for 3 and 190 nM and 3.9 microM for 4), indicating that these peptides can act at the early stages of HIV-1 entry. The potent activity of depsipeptides containing the glycosylated beta-OMe Tyr unit demonstrates that beta-OMe Tyr itself is not critical for activity. Mirabamides A-C inhibited the growth of B. subtilis and C. albicans at 1-5 microg/disk in disk diffusion assays.

Continuing our investigations on plants belonging to the Asclepiadaceae family, three new cardenolide glycosides, 3'-O-beta-D-glucopyranosylcalactin (1), 12-dehydroxyghalakinoside (2), and 6'-dehydroxyghalakinoside (3), along with the known ghalakinoside (4) and calactin (5), were isolated from the roots of Pergularia tomentosa. The structures of these compounds were elucidated by extensive spectroscopic methods including 1D- and 2D-NMR experiments as well as ESIMS analysis. The isolated cardenolides caused apoptotic cell death of Kaposi's sarcoma cells.