Isabelle Bonnard

Total structure and biological properties of laxaphycins A and B, cyclic lipopeptides from the marine cyanobacterium Lyngbya majuscula

The tropical marine cyanobacteriumLyngbya majuscula produces a series of cytotoxic and antimicrobial cyclic peptides. The total structure of the two major components, laxaphycins A and B, was determined by interpretation of physical data, principally high field NMR, FAB MS and MS/MS, in combination with chemical derivatization and degradation schemes. Absolute stereochemistries of the natural and ‘exotic’ amino acids were determined. The two cyclic peptides exhibited an unusual biological synergism when tested for antifungal or cytotoxic effects.

New Lobane and Cembrane Diterpenes from Two Comorian Soft Corals

Preliminary biological investigation of a collection of Comorian soft corals resulted in the selection of two specimens, one of Sarcophyton and the other of Lobophytum, on the basis of their toxicity on larvae of the brine shrimp (Artemia salina) and inhibition of acetylcholinesterase, respectively. Bioassay-guided fractionations provided a known antitumor promoter cembrane diterpenoid, (+)-sarcophytol-A (1), along with a new lobane diterpenoid, carbomethoxyfuscol (2), from Sarcophyton sp., and a new cembranoid, crassumolide E (3), from Lobophytum sp. The structures of compounds 1–3 were determined by spectroscopic analysis and by comparison of the spectral data with previously reported values. The cembranoid 3 was found to exhibit a moderate inhibitory effect on acetylcholinesterase.

Cystodamine, a new cytotoxic fused polyaromatic alkaloid from the Mediterranean ascidian Cystodytes delle chiajei

Abstract a fused pentacyclic aromatic alkaloid - cystodamine - was isolated from a Mediterranean ascidian Cystodytes delle chiajei (Polycitoridae). The structure, determinated by extensive 2D-NMR means, is the first example of a marine product displaying a 1 H- 14 N coupling during 1 H NMR analysis.

Tyr5didemnin B and [D-Pro4]didemnin B; Two new natural didemnins with a modified macrocycle

Abstract The structures of the two natural didemnins with a modified macrocycle, [Tyr5]didemnin B [2] and [D-Pro4]didemnin B [3], isolated from the Aplousobranch ascidian Trididemnum cyanophorum (Didemnidae) are described. Structures were determined by FABMS and NMR spectroscopy, absolute configurations by Marfey analysis of the acid hydrolisatcs. Conformational informations arc given and cytotoxic activities against human lymphoblastic leukemia cell lines evaluated.

First total synthesis and stereochemical revision of laxaphycin B and its extension to lyngbyacyclamide A.

The first total synthesis of laxaphycin B was accomplished through stepwise automated Solid Phase Peptide Synthesis (SPPS), leading to the structural revision of its stereochemistry especially with regard to the configuration of one of the two 3-hydroxyleucines of this cyclic dodecapeptide of marine origin. The analogous Lyngbyacyclamide A was obtained by an extension of this synthesis.

[Hysp2] and [Hap2]Didemnin B, two new [Hip2]-modified didemnin B from the tunicate Trididemnum cyanophorum

The structures of two new didemnins ([Hysp2]didemnin B and [Hap2]didemnin B) from the Aplousobranch ascidian Trididemnum cyanophorum (Didemnidae) are described. Structures are determined by a combination of mass spectrometry and one and two-dimensional high-field NMR techniques. Complete 1H and 13C NMR spectral assignments and conformational informations are presented. The cytotoxicities of the compounds towards drug-sensitive and drug-resistant tumor cell lines are compared with those of didemnins A and B.

Isolation and Synthesis of Laxaphycin B-Type Peptides: A Case Study and Clues to Their Biosynthesis

The laxaphyci’s B family constitutes a group of five related cyclic lipopeptides isolated from diverse cyanobacteria from all around the world. This group shares a typical structure of 12 amino acids from the l and d series, some of them hydroxylated at the beta position, and all containing a rare beta-amino decanoic acid. Nevertheless, they can be differentiated due to slight variations in the composition of their amino acids, but the configuration of their alpha carbon remains conserved. Here, we provide the synthesis and characterization of new laxaphycin B-type peptides. In doing so we discuss how the synthesis of laxaphycin B and analogues was developed. We also isolate minor acyclic laxaphycins B, which are considered clues to their biosynthesis.

Structures and Activities of Tiahuramides A–C, Cyclic Depsipeptides from a Tahitian Collection of the Marine Cyanobacterium Lyngbya majuscula

The structures of three new cyclic depsipeptides, tiahuramides A (1), B (2), and C (3), from a French Polynesian collection of the marine cyanobacterium Lyngbya majuscula are described. The planar structures of these compounds were established by a combination of mass spectrometry and 1D and 2D NMR experiments. Absolute configurations of natural and nonproteinogenic amino acids were determined through a combination of acid hydrolysis, derivitization with Marfeys reagent, and HPLC. The absolute configuration of hydroxy acids was confirmed by Moshers method. The antibacterial activities of tiahuramides against three marine bacteria were evaluated. Compound 3 was the most active compound of the series, with an MIC of 6.7 μM on one of the three tested bacteria. The three peptides inhibit the first cell division of sea urchin fertilized eggs with IC50 values in the range from 3.9 to 11 μM. Tiahuramide B (2), the most potent compound, causes cellular alteration characteristics of apoptotic cells, blebbing, DNA condensation, and fragmentation, already at the first egg cleavage. The cytotoxic activity of compounds 1-3 was tested in SH-SY5Y human neuroblastoma cells. Compounds 2 and 3 showed an IC50 of 14 and 6.0 μM, respectively, whereas compound 1 displayed no toxicity in this cell line at 100 μM. To determine the type of cell death induced by tiahuramide C (3), SH-SY5Y cells were costained with annexin V-FITC and propidium iodide and analyzed by flow cytometry. The double staining indicated that the cytotoxicity of compound 3 in this cell line is produced by necrosis.