Isabelle Grondin

Antiviral Activity of Flexibilane and Tigliane Diterpenoids from Stillingia lineata

In an effort to identify new potent and selective inhibitors of chikungunya virus and HIV-1 and HIV-2 virus replication, the endemic Mascarene species Stillingia lineata was investigated. LC/MS and bioassay-guided purification of the EtOAc leaf extract using a chikungunya virus-cell-based assay led to the isolation of six new (4-9) and three known (1-3) tonantzitlolones possessing the rare C20-flexibilane skeleton, along with tonantzitloic acid (10), a new linear diterpenoid, and three new (11, 13, and 15) and two known (12 and 14) tigliane-type diterpenoids. The planar structures of the new compounds and their relative configurations were determined by spectroscopic analysis, and their absolute configurations were determined through comparison with literature data and from biogenetic considerations. These compounds were investigated for selective antiviral activity against chikungunya virus (CHIKV), Semliki Forest virus, Sindbis virus, and, for compounds 11-15, the HIV-1 and HIV-2 viruses. Compounds 12-15 were found to be the most potent and are selective inhibitors of CHIKV, HIV-1, and HIV-2 replication. In particular, compound 14 inhibited CHIKV replication with an EC50 value of 1.2 μM on CHIKV and a selectivity index of >240, while compound 15 inhibited HIV-1 and HIV-2 with EC50 values of 0.043 and 0.018 μM, respectively. It was demonstrated further that potency and selectivity are sensitive to the substitution pattern on the tigliane skeleton. The cytotoxic activities of compounds 1-10 were evaluated against the HCT-116, MCF-7, and PC3 cancer cell lines.

Insecticidal Activity of the Leaf Essential Oil of Peperomia borbonensis Miq. (Piperaceae) and Its Major Components against the Melon Fly Bactrocera cucurbitae (Diptera: Tephritidae)

The essential oil from the leaves of Peperomia borbonensis from Réunion Island was obtained by hydrodistillation and characterized using GC‐FID, GC/MS and NMR. The main components were myristicin (39.5%) and elemicin (26.6%). The essential oil (EO) of Peperomia borbonensis and its major compounds (myristicin and elemicin), pure or in a mixture, were evaluated for their insecticidal activity against Bactrocera cucurbitae (Diptera: Tephritidae) using a filter paper impregnated bioassay. The concentrations necessary to kill 50% (LC50) and 90% (LC90) of the flies in three hours were determined. The LC50 value was 0.23 ± 0.009 mg/cm2 and the LC90 value was 0.34 ± 0.015 mg/cm2 for the EO. The median lethal time (LT50) was determined to compare the toxicity of EO and the major constituents. The EO was the most potent insecticide (LT50 = 98 ± 2 min), followed by the mixture of myristicin and elemicin (1.4:1) (LT50 = 127 ± 2 min) indicating that the efficiency of the EO is potentiated by minor compounds and emphasizing one of the major assets of EOs against pure molecules.

Exploring the chemodiversity of tropical microalgae for the discovery of natural antifouling compounds

Marine microalgae and cyanobacteria have largely been studied for their biotechnological potential and proved their ability to produce a wide array of bioactive molecules. We investigated the antifouling potential of unexplored benthic tropical microalgae using anti-adhesion and toxicity bioassays against two major micro- and ma crobiofoulers, namely bacteria and barnacles. Fifty strains belonging to six phyla [Cyanobacteria, Miozoa (Dinoflagellata), Bacillariophyta, Cryptophyta, Rhodophyta and Haptophyta] were isolated from southwestern Islands of the Indian Ocean. They were chosen in order to represent as much as possible the huge biodiversity of such a rich tropical ecosystem. The associated chemodiversity was highlighted by both NMR- and LC-MS-based metabolomics. The screening of 84 algal fractions revealed that the anti-adhesion activity was concentrated in methanolic ones (i.e. 93% of all active fractions). Our results confirmed that microalgae constitute a promising source of natural antimicrofoulants as 17 out of the 30 active fractions showed high or very high capacity to inhibit the adhesion of three biofilm-forming marine bacteria. Dinoflagellate-derived fractions were the most active, both in terms of number and intensity. However, dinoflagellates were also more toxic and may not be suitable as a source of environmentally friendly antifouling compounds, in contrast to diatoms, e.g. Navicula mollis. The latter and two dinoflagellates of the genus Amphidinium also had interesting anti-settlement activities while being moderately toxic to barnacle larvae. Our approach, combining the bioprospecting of a large number of tropical microalgae for their anti-settlement potential and metabolomics analyses, constituted a first step towards the discovery of alternative ecofriendly antifoulants.

N-myristoyltransferases inhibitory activity of ellagitannins from Terminalia bentzoë (L.) L. f. subsp. bentzoë

N-myristoylation (Myr) is an eukaryotic N-terminal co- or post-translational protein modification in which the enzyme N-myristoyltransferase (NMT) transfers a fatty acid (C14:0) to the N-terminal glycine residues of several cellular key proteins. Depending on the cellular context, NMT may serve as a molecular target in anticancer or anti-infectious therapy, and drugs that inhibit this enzyme may be useful in the treatment of cancer or infectious diseases. As part of an on-going project to identify natural Homo sapiens N-myristoyltransferase 1 inhibitors (HsNMT1), two ellagitannins, punicalagin (1) and isoterchebulin (2), along with eschweilenol C (3) and ellagic acid (4) were isolated from the bark of Terminalia bentzoë (L.) L. f. subsp. bentzoë. Their structures were determined by means of spectroscopic analyses and comparison with literature data. Punicalagin (1) and isoterchebulin (2) showed significant inhibitory activity towards HsNMT1, and also against Plasmodium falciparum NMT (PfNMT) both in vitro and in cellulo, opening alternative paths for new NMT inhibitors development. This is the first report identifying natural products from a botanical source as inhibitors of HsNMT and PfNMT.