Antiparasitic Ovalicin Derivatives from Pseudallescheria boydii, a Mutualistic Fungus of French Guiana Termites.

Social insects are in mutualism with microorganisms, contributing to their resistance against infectious diseases. The fungus Pseudallescheria boydii SNB-CN85 isolated from termites produces ovalicin derivatives resulting from the esterification of the less hindered site of the ovalicin epoxide by long-chain fatty acids. Their structures were elucidated using spectroscopic analysis and semisynthesis from ovalicin. For ovalicin, these compounds displayed antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei, with IC50 values of 19.8 and 1.1 µM, respectively, for the most active compound, i.e., ovalicin linoleate. In parallel, metabolomic profiling of a collection of P. boydii strains associated with termites made it possible to highlight this class of compounds together with tyroscherin derivatives in all strains. Finally, the complete genome of P. boydii strains was obtained by sequencing, and the cluster of potential ovalicin and ovalicin biosynthesis genes was annotated. Through these metabolomic and genomic analyses, a new ovalicin derivative named boyden C, in which the 6-membered ring of ovalicin was opened by oxidative cleavage, was isolated and structurally characterized.

Alsinol, an arylamino alcohol derivative active against Plasmodium, Babesia, Trypanosoma, and Leishmania: past and new outcomes.

Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested against Plasmodium, Babesia, Trypanosoma, and Leishmania. In silico Alsinol follows the Lipinski and Ghose rules. In vitro it had schizontocidal activity against Plasmodium falciparum and was able to inhibit gametocytogenesis; it was particularly active against late gametocytes. In malaria-infected mice, it showed a dose-dependent activity similar to chloroquine. It demonstrated a similar level of activity to reference compounds against Babesia divergens, and against promastigotes, and amastigotes stages of Leishmania in vitro. It inhibited the in vitro growth of two African animal strains of Trypanosoma but was ineffective in vivo in our experimental conditions. It showed moderate toxicity in J774A1 and Vero cell models. The study demonstrated that Alsinol has a large spectrum of activity and is potentially affordable to produce. Nevertheless, challenges remain in the process of scaling up synthesis, creating a suitable clinical formulation, and determining the safety margin in preclinical models.

Potent and Non-Cytotoxic Antibacterial Compounds Against Methicillin-Resistant Staphylococcus aureus Isolated from Psiloxylon mauritianum, A Medicinal Plant from Reunion Island.

With the occurrence of antibiotic-resistant Staphylococcus aureus strains, identification of new anti-staphylococcal drugs has become a necessity. It has long been demonstrated that plants are a large and diverse source of antibacterial compounds. Psiloxylon mauritianum, an endemic medicinal plant from Reunion Island, was chemically investigated for its reported biological activity against S. aureus. Aspidin VB, a phloroglucinol derivative never before described, together with Aspidin BB, were first isolated from the ethyl acetate extract of P. mauritianum leaves. Their structures were elucidated from spectroscopic data. Aspidin VB exhibited strong antibacterial activity against standard and methicillin-resistant S. aureus strains, with a minimal inhibition concentration (MIC) of 0.25 µg/mL, and no cytotoxicity was observed at 10-5 M in MRC5 cells. Due to its biological activities, Aspidin VB appears to be a good natural lead in the fight against S. aureus.

Modified Clerodanes from the Essential Oil of Dodonea viscosa Leaves.

Dodonea viscosa (L.) Jacq from Reunion Island (Indian Ocean) was investigated for its leaf essential oil composition. The plant was extracted by hydrodistillation and its essential oil analysed by gas chromatography coupled to mass spectrometry. This study revealed that oxygenated nor-diterpenes and diterpenes were one of the major chemical classes (> 50%) mainly consisting of three modified cyclopropylclerodanes containing a bicyclo[5.4.0]undecane ring system: one new furanoid norditerpene, dodovisate C, and two furanoid diterpenes, the known methyl dodovisate A and the new methyl iso-dodovisate A. These three compounds were isolated by liquid chromatography and their structures established on the basis of spectroscopic studies. The absolute configuration of dodovisate C was elucidated through a joint experimental and theoretical (B3LYP/6-311+G(d,p)) electronic circular dichroism study. The relative configurations of methyl dodovisate A and methyl iso-dodovisate A were determined using linear regressions of theoretical chemical shifts versus experimental values with the (B3LYP/6-311+G(d,p)) method.

Netamines O-S, Five New Tricyclic Guanidine Alkaloids from the Madagascar Sponge Biemna laboutei, and Their Antimalarial Activities.

In our continuing program to isolate new compounds from the Madagascar sponge Biemna laboutei, five new tricyclic guanidine alkaloids, netamines O - S (1-5, resp.), have been identified together with the known compounds netamine E (6) and mirabilin J (7). The structures of all new netamines were assigned on the basis of spectroscopic analyses. Their relative configurations were established by analysis of ROESY data and comparison with literature data. Netamines O, P, and Q, which were isolated in sufficient quantities, were tested for their cytotoxic activities against KB cells and their activities against the malaria parasite Plasmodium falciparum. Netamines O and Q were found to be moderately cytotoxic. Netamines O, P, and Q exhibited antiplasmodial activities with IC50 values of 16.99 ± 4.12, 32.62 ± 3.44, and 8.37 ± 1.35 µM, respectively.

Netamines H-N, tricyclic alkaloids from the marine sponge Biemna laboutei and their antimalarial activity.

Chemical examination of the CH2Cl2-MeOH (1:1) extract of the Madagascar sponge Biemna laboutei resulted in the isolation of seven new tricyclic alkaloids, netamines H-N (1-7), along with the known netamine G and mirabilins A, C, and F. Their structures were elucidated by interpretation of 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their cytotoxicity against KB cells and their antiplasmodial activity. Netamine M (6) was found to be cytotoxic, with an IC50 value in the micromolar range, and netamine K (4) exhibited activity against Plasmodium falciparum with an IC50 value of 2.4 µM.

Pipestelides A-C: cyclodepsipeptides from the Pacific marine sponge Pipestela candelabra.

Pipestelides A-C (2-4) are three new NRPS-PKS hybrid macrolides containing uncommon moieties, isolated from the Pacific marine sponge Pipestela candelabra. Their structures were elucidated on the basis of spectroscopic data. These cyclodepsipeptides appear to be biosynthetically related to jaspamide (aka jasplakinolide) (1) by chemical modification of the building blocks of the polyketide or peptide chains. Pipestelides A-C (2-4) contain a bromotyrosine [3-amino-3-(bromo-4-hydroxyphenyl)propanoic acid] unit, a polypropionate with a Z double bond, and a 2-hydroxyquinolinone, respectively. Revised chemical shift assignments are provided for the co-isolated known jasplakinolide C(a) (5). In addition, compounds 2 and 3 exhibited cytotoxic activities in the micromolar range.

Agelastatin E, agelastatin F, and benzosceptrin C from the marine sponge Agelas dendromorpha.

The study of the n-butanol extract of the New Caledonian sponge Agelas dendromorpha led to the isolation and identification of three new pyrrole-2-aminoimidazole (P-2-AI) alkaloids, named agelastatins E (3) and F (4) and benzosceptrin C (5), together with 10 known metabolites, agelastatin A (1), agelastatin D (2), sceptrin (6), manzacidin A, tauroacidin A, taurodispacamide A, nortopsentin D, thymine, longamide, and 4,5-dibromopyrrole-2-carboxamide. Their structures were assigned by spectroscopic data interpretation. All the compounds were tested for cytotoxic activity.

Assessment of antioxidant and dermoprotective activities of gold nanoparticles as safe cosmetic ingredient.

Hubertia ambavilla, an endemic plant originating from Reunion Island in the Indian Ocean, is traditionally used as an anti-inflammatory and in healing, both for internal and external use. Polyphenolic compounds from aqueous phase extractions can reduce metal salts into nanoparticles and stabilize them in one step. Although gold nanoparticles are well described in the literature as anti-ageing ingredients, the nanoparticles presented herein are novel and are synthesized using a green process. We demonstrate their efficiency as dermoprotective, free radical scavenger and antioxidant cosmetic ingredients. Comparison with common nanoparticles obtained by the Turkevich method clearly emphasizes the necessity to carefully screen the products used for nanoparticle coatings, as they play a major role in the biological properties of the product. Hubertia ambavilla mediated gold nanoparticles are non-toxic to human dermal fibroblasts, possess free radical scavenging potential, and protect against damage to fibroblast and dermal cells caused by ultraviolet A radiation.

Ilicicolinic acids and ilicicolinal derivatives from the fungus Neonectria discophora SNB-CN63 isolated from the nest of the termite Nasutitermes corniger found in French Guiana show antimicrobial activity.

The fungus Neonectria discophora SNB-CN63 has been isolated from the nest of the termite Nasutitermes corniger found in French Guiana. From the ethyl acetate extract of fungal culture, bioassay guided fractionation led to the isolation of fourteen ilicicolinic acids and ilicicolinal derivatives. Their structures were elucidated by analyses of 1D and 2D NMR and MS spectroscopic data. All metabolites were tested against several microbial pathogens and six displayed antimicrobial activities with MIC <16 µg/mL on T. rubrum, Staphylococcus aureus and methicillin-resistant S. aureus. Based on their structural similarities, a common biosynthetic pathway is proposed for all isolated metabolites.

Mucorolactone, a Macrolactone from Mucor sp. SNB-VECD13A, a Fungus Isolated from the Cuticle of a Vespidae Species.

The newly discovered macrolactone, mucorolactone, along with eight known compounds, was isolated from an ethyl acetate extract of the insect-borne fungus Mucor sp. All structures were elucidated using 1D and 2D NMR and MS spectroscopic experiments. Relative and absolute configurations of the original skeleton of mucorolactone was deduced from NOESY experiments, from the 13C NMR chemical shift calculation based on the DP4 probability method, and from the comparison of experimental and calculated electronic circular dichroism spectra.

Pseudallicins A-D: Four Complex Ovalicin Derivatives from Pseudallescheria boydii SNB-CN85.

The isolation and complete structural elucidation of four complex ovalicin analogues, named pseudallicins A-D, from the fungus Pseudallescheria boydii strain SNB-CN85 are described. On the basis of structural similarities and information from the literature, a joint biosynthetic pathway for the pseudallicins is proposed.

Large Diversity and Original Structures of Acyl-Homoserine Lactones in Strain MOLA 401, a Marine Rhodobacteraceae Bacterium.

Quorum sensing (QS) is a density-dependent mechanism allowing bacteria to synchronize their physiological activities, mediated by a wide range of signaling molecules including N-acyl-homoserine lactones (AHLs). Production of AHL has been identified in various marine strains of Proteobacteria. However, the chemical diversity of these molecules still needs to be further explored. In this study, we examined the diversity of AHLs produced by strain MOLA 401, a marine Alphaproteobacterium that belongs to the ubiquitous Rhodobacteraceae family. We combined an original biosensors-based guided screening of extract microfractions with liquid chromatography coupled to mass spectrometry (MS), High Resolution MS/MS and Nuclear Magnetic Resonance. This approach revealed the unsuspected capacity of a single Rhodobacteraceae strain to synthesize 20 different compounds, which are most likely AHLs. Also, some of these AHLs possessed original features that have never been previously observed, including long (up to 19 carbons) and poly-hydroxylated acyl side chains, revealing new molecular adaptations of QS to planktonic life and a larger molecular diversity than expected of molecules involved in cell-cell signaling within a single strain.

Boric acid: a highly efficient catalyst for transamidation of carboxamides with amines.

A novel method of transamidation of carboxamides with amines using catalytic amounts of readily available boric acid under solvent-free conditions has been developed. The scope of the methodology has been demonstrated with (i) primary, secondary, and tertiary amides and phthalimide and (ii) aliphatic, aromatic, cyclic, acyclic, primary, and secondary amines.