Endophytic biocatalysts with enoate reductase activity isolated from Mentha pulegium.

The biotransformation of (4R)-(-)-carvone by Mentha pulegium (pennyroyal) leaves and its endophytic bacteria was performed in order to search for novel biocatalysts with enoate reductase activity. The obtained results clearly indicated that endophytes play an important role in the biotransformation of (4R)-(-)-carvone with pennyroyal plant tissues. The best activity was associated to the endophytic bacteria Pseudomonas proteolytica FM18Mci1 and Bacillus sp. FM18civ1. Enoate reductase activity for the reduction of (4R)-(-)-carvone and (4S)-(+)-carvone as model substrates was evaluated for each strain. Finally, both isolated strains were evaluated for the kinetic resolution of racemic carvone. The two bacteria gave (1R, 4R) or (1R, 4S)-dihydrocarvone as major products. P. proteolytica FM18Mci1 had preference for the 4S-(-)-carvone, reaching a conversion 95% in 24 h. In contrast, Bacillus sp. FM18civ1 had preference for (4R)-(-)-carvone. The results obtained in the kinetic resolution of carvone indicated that the Bacillus strain could be useful for resolving a racemic mixture of carvone.

Anticancer effect of altersolanol A, a metabolite produced by the endophytic fungus Stemphylium globuliferum, mediated by its pro-apoptotic and anti-invasive potential via the inhibition of NF-κB activity.

Altersolanol A, a natural product from the endophytic fungus Stemphylium globuliferum isolated from the medicinal plant Mentha pulegium (Lamiaceae) growing in Morocco, shows cytotoxic, cytostatic, anti-inflammatory and anti-migrative activity against human chronic myeloid K562 leukemia and A549 lung cancer cells in a dose dependent manner without affecting the viability of non cancerous cells. Altersolanol A induces cell death by apoptosis through the cleavage of caspase-3 and -9 and through the decrease of anti-apoptotic protein expression. Moreover, we report here the importance of the distinct structural features of altersolanol A by testing other related anthracene derivatives in order to identify preliminary structure-activity relationships. Acetylation of altersolanol A did not improve activity where other derivatives such as tetrahydroaltersolanol B and ampelanol that differ from altersolanol A by reduction of one of a carbonyl group and removal of hydroxyl substituents were inactive in comparison. Altogether our results suggest that altersolanol A may be considered as an interesting lead for further development of chemotherapeutic agents.

Bioactive metabolites from the endophytic fungus Stemphylium globuliferum isolated from Mentha pulegium.

The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded five new secondary metabolites, alterporriol G (4) and its atropisomer alterporriol H (5), altersolanol K (11), altersolanol L (12), stemphypyrone (13), and the known compounds 6-O-methylalaternin (1), macrosporin (2), altersolanol A (3), alterporriol E (6), alterporriol D (7), alterporriol A (8), alterporriol B (9), and altersolanol J (10). The structures were determined on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. Among the alterporriol-type anthranoid dimers, the mixture of alterporriols G and H (4/5) exhibited considerable cytotoxicity against L5178Y cells with an EC(50) value of 2.7 microg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for kinase inhibitory activity in an assay involving 24 different kinases. Compounds 1, 2, 3, and the mixture of 4 and 5 were the most potent inhibitors, displaying EC(50) values between 0.64 and 1.4 microg/mL toward individual kinases.