Zygosporamide, a cytotoxic cyclic depsipeptide from the marine-derived fungus Zygosporium masonii

Zygosporamide (1), a new cyclic pentadepsipeptide, was isolated from the seawater-based fermentation broth of a marine-derived fungus identified as Zygosporium masonii. The structure of 1, which is composed of α-hydroxyleucic acid and both d- and l-amino acids, was determined by combined spectral and chemical methods. Despite a simple structure, zygosporamide illustrated significant cytotoxicity in the NCI’s 60 cell line panel (median GI₅₀ = 9.1 μM), with highly enhanced selectivity against the CNS cancer cell line SF-268 (GI₅₀ = 6.5 nM) and the renal cancer cell line RXF 393 (GI₅₀ ? 5.0 nM).     

Stereoselective total synthesis of arenastatin A, a spongean cytotoxic depsipeptide

A highly stereoselective total synthesis of arenastatin A, an extremely potent cytotoxic cyclic depsipeptide from marine sponge, was developed. The desired 7,8-β-epoxide in arenastatin A was constructed by asymmetric sulfur ylide-mediated epoxidation in good yield and highly stereoselective manner.     

Two polypropionate metabolites from the cephalaspidean mollusk Philinopsis speciosa

Two polypropionate compounds, niuhinone-A and -B were isolated from a mollusk, $\text{Philinopsis speciosa}$, and their structures were elucidated by spectral methods.     

Isolation, structure, and synthesis of dolastatin D, a cytotoxic cyclic depsipeptide from the sea gare Dolabella auricularia

Dolastatin D (1), a cytotoxic cyclic depsipeptide possessing the novel β-amino acid (2R,3R)-3-amino-2-methylbutanoic acid [(2R,3R]-3] as a component, has been isolated from the Japanese sea hare Dolabella auricularia. The absolute stereostructure of 1 was elucidated on the basis of spectroscopic analysis and chemical degradation and was further confirmed by synthesis.     

Aurilide, a cytotoxic depsipeptide from the sea hare Dolabella auricularia: isolation, structure determination, synthesis, and biological activity

The bioassay-guided fractionation of the cytotoxic constituents of the Japanese sea hare Dollabella auricularia led to the isolation of aurilide (1), a 26-membered cyclodepsipeptide. The gross structure of 1 was established by spectroscopic analysis including 2D NMR techniques. The absolute stereostructure was determined by chiral HPLC analysis of acid hydrolysates of 1 and by the enantioselective synthesis of a degradation product arising from a dihydroxylated fatty acid portion. The enantioselective synthesis of 1 was achieved in 12% overall yield (16 steps) and confirmed the absolute stereostructure of 1. The cytotoxicity of 1 was evaluated using a synthetic sample, which was found to exhibit potent cytotoxicity against HeLa S₃ cells with an IC₅₀ of 0.011 μg/mL. Further biological and pharmacological studies of 1 have been carried out by using synthetic 1.     

Major terpenoids from Telekia speciosa flowers and their cytotoxic activity in vitro

In addition to known constituents of Telekia speciosa, an acetone extract from ray florets of the plant yielded: 5,5?-dibutoxy-2,2?-bifuran (1), 5,5?-diisobutoxy-2,2?-bifuran (2), α-tocopherol (3), β-tocopherol (4), loliolide palmitate (5), a mixture of calenduladiol esters - 16β-hydroxylupeol-3-O-palmitate (7) and 16β-hydroxylupeol-3-O-myristate (8), 1-epiinuviscolide (12), inuviscolide (13), 3-epiisotelekin (16), 4α-hydroxy-9β,10β-epoxy-1β(H)-11(13)-guaien-8α,12-olide (17), 4α-hydroxy-1β(H)-9(10),11(13)-guaiadien-8α,12-olide (18), loliolide (19) and 4β,10β-dihydroxy-1α(H),5α(H)-11(13)-guaien-8α,12-olide (20). Calenduladiol esters and asperilin (14) were the major constituents of the extract. Their cytotoxic effect on human normal prostate epithelial cells (PNT-2), human prostate carcinoma cell lines, human skin fibroblasts (HSF) and human melanoma cell lines was examined in vitro. Triterpene esters showed no cytotoxicity against nearly all cell lines tested, except for Du145 prostate carcinoma cells (IC₅₀ – 62.0 μΜ). Asperilin displayed activity against the cell lines under study, especially against three tested lines of melanomas (A375, IC₅₀ – 17.6 μΜ, WM793, IC₅₀ – 28.2 μΜ and Hs 294T, IC₅₀ – 29.5 μΜ).     

Kyanamide,a new Ahp-containing depsipeptide from marine cyanobacterium Caldora penicillata

Kyanamide (1), a new depsipeptide containing 3-amino-6-hydroxy-2-piperidone moiety, was isolated from the Caldora penicillata marine cyanobacterium collected in Okinawa. Its structure was determined by spectroscopic analysis and Marfey's analysis of acid hydrolysate. Kyanamide exhibited moderate cytotoxicity against HeLa S3 cells. 1 also exhibited potent protease inhibitory activity against elastase and chymotrypsin with IC₅₀ values of 0.13 nM and 1.1 μM.     

Coibamide A, a potent antiproliferative cyclic depsipeptide from the Panamanian marine cyanobacterium Leptolyngbya sp

Coibamide A (1) is a new, potent antiproliferative depsipeptide which was isolated from a marine Leptolyngbya cyanobacterium collected from the Coiba National Park, Panama. The planar structure of 1 was elucidated by a combination of NMR spectroscopy and mass spectrometry. Exhaustive 1D and 2D NMR spectroscopy included natural abundance 15N and variable temperature experiments; mass spectrometry included TOF-ESI-MSn and FT-MSn experiments. Chemical degradation followed by chiral HPLC- and GC-MS analyses was used to assign the absolute configuration of 1. This highly methylated cyclized depsipeptide exhibited an unprecedented selectivity profile in the NCI 60 cancer cell line panel and appears to act via a novel mechanism.     

Stereocalpin A, a bioactive cyclic depsipeptide from the Antarctic lichen Stereocaulon alpinum

A new cyclic depsipeptide stereocalpin A (1) has been isolated from the MeOH extract of the Antarctic lichen Stereocaulon alpinum by various chromatographic methods. The structure of stereocalpin A (1) was mainly determined by analysis of the NMR spectroscopic data and by chemical methods. Stereocalpin A (1) is a unique cyclic peptide incorporating an unprecedented 5-hydroxy-2,4-dimethyl-3-oxo-octanoic acid in the structure. Stereocalpin A (1) shows moderate cytotoxicity against three human solid tumor cell lines.     

Nagahamide A,an antibacterial depsipeptide from the marine sponge Theonella swinhoei

[structure: see text] An antibacterial depsipeptide, nagahamide A (1), has been isolated from the marine sponge Theonella swinhoei. Its structure was determined on the basis of spectral and chemical methods. Absolute configuration of amino acid residues was determined by Marfey's analysis, and relative stereochemistry of the polyketide moiety was assigned by comparison of NMR data with those of a model compound.     

Model depsipeptide derivatives from 2-bromo-N-benzylisobutyramide

2-Bromo-N-benzylisobutyramide reacts with N-protected aminoacids in the presence of silver oxide to afford the pertinent depsipeptide derivatives in mild conditions, high yields and short time.     

Aglajne-1, a polypropionate metabolite from the opisthobranch mollusk Aglaja depicta: Determination of carbon-carbon connectivity via long-range 1H-13C couplings

The structure of Aglajane-1, a polypropionate metabolite extracted from the opisthobranch $\text{Aglaja depicta}$, has been determined by extensive use of 2D-NMR and confirmed on chemical grounds.     

Iriomoteolide-1a, a potent cytotoxic 20-membered macrolide from a benthic dinoflagellate amphidinium species

A potent cytotoxic 20-membered macrolide, iriomoteolide-1a (1), has been isolated from a benthic dinoflagellate Amphidinium sp. (strain HYA024), and the structure was elucidated on the basis of detailed analyses of 2-D NMR data. The relative and absolute stereochemistries were assigned by the combination of conformational analyses using NMR data and modified Mosher's method of 1.     

Marcanine G,a new cytotoxic 1-azaanthraquinone from the stem bark of Goniothalamus marcanii Craib

The ethanolic extract from the stem bark of Goniothalamus marcanii Craib was shown in preliminary brine shrimp lethality data having good cytotoxic activity. Further bioassay guided isolation was done by means of solvent partition, chromatography and precipitation to provide four isolated compounds: a novel compound 1 with the core structure of 1-azaanthraquinone moiety referred as marcanine G; as well as compounds 2–4 with known aristolactam structures namely, piperolactam C, cepharanone B and taliscanine. These compounds were characterised by spectroscopic techniques. The assessment of cytotoxicity was established on an SRB assay using doxorubicin as a positive control. Marcanine G (1) was considered the most active compound indicating the IC₅₀ values of 14.87 and 15.18 μM against human lung cancer cells (A549) and human breast cancer cells (MCF7), respectively. However, 2 showed mild activity with the IC₅₀ values of 83.72 and 82.32 μM against A549 and MCF7 cells, respectively.     

Isolation, structure, and synthesis of dolastatin C, a new depsipeptide from the sea hare Dolabella auricularia

Dolastain C (1), a new depsipeptide exhibiting weak cytotoxicity, has been isolated from the Japanese sea hare Dolabella auricularia. The structure of 1 was elucidated by spectroscopic analysis and chemical degradation. The synthesis of 1 was carried out to confirm the structure unambiguously.     

Gymnangiamide, a cytotoxic pentapeptide from the marine hydroid Gymnangium regae

A cytotoxic aqueous extract from the marine hydroid Gymnangium regae provided a novel linear pentapeptide, designated gymnangiamide (1). The planar structure of 1 was elucidated by interpretation of spectral data as well as chemical degradation and derivatization studies. In addition to the amino acids isoleucine and phenylserine, this peptide contained N-desmethyldolaisoleuine, O-desmethyldolaproine, and alpha-guanidino serine, three residues that have not previously been reported in a natural product. The absolute configurations of the constituent amino/guanidino acids were determined by chemical degradation and derivatization, followed by HPLC and LC-MS comparison with authentic standards. Gymnangiamide (1) was moderately cytotoxic against a number of human tumor cell lines in vitro.     

Duryne,a new cytotoxic agent from the marine sponge Cribrochalinadura

Duryne, 1, a cytotoxic metabolite which inhibits the growth of both mouse and human tumor cell lines invitro has been isolated from the marine sponge Cribrochalinadura. Its structure has been assigned by spectral methods.     

Szentiamide, an N-formylated cyclic depsipeptide from Xenorhabdus szentirmaii DSM 16338T

Szentiamide (1) a new cyclic hexadepsipeptide was isolated from the culture broth of the entomopathogenic bacterium Xenorhabdus szentirmaii DSM 16338T. The structure was elucidated by analysis of one- and two-dimensional NMR spectra and high resolution mass spectrometry. The amino acids were determined to be D-leucine, L-threonine, D-phenylalanine, D-valine, L-tyrosine and L-tryptophane after hydrolysis and derivatization with D-FDVA [Nalpha-(2,4-dinitro-5-fluorophenyl)-D-valinamide].