4-Hydroxyalternariol 9-methyl ether

We report the isolation and characterization of five polyketides [alternariol (1), alternariol-9-methyl ether (2), altertoxin I (3), altertoxin II (4) and tenuazonic acid (5)] from the marine endophytic Alternaria sp. LV52 derived from Cystoseira tamariscifolia, collected from the Red Sea at Nabq-Bay, Egypt. The chemical structures of compounds 1-5 were identified by extensive 1D, 2D NMR, and HR mass measurements. Isolation and phenotypic and genotypic characterization of the producing fungus is reported. The antimicrobial activity of the produced extract and derived compounds was examined against a panel of test organisms. In addition, an in vitro cytotoxic activity of 1-5 was performed against diverse cancer cell lines: HEPG2, HELA, A549 and PC3, revealing that compounds 2 and 4 are potentially cytotoxic against A549 and PC3 with EC50 of 0.73 µg/ml (2.69 µM) and 0.17 µg/ml (0.64 µM) for 2, and 0.40 µg/ml (1.15 µM) and 0.12 µg/ml (0.33 µM) for 4, respectively.

The EtOAc extract of the liquid fermentation of Alternaria sp. Samif01, an endophytic fungus obtained from Salvia miltiorrhiza Bunge, showed antibacterial activity against several tested bacterial pathogens. Fractionation of this extract led to the isolation of seven dibenzo-α-pyrones (1-7), including one new compound, 2-acetoxy-2-epi-altenuene (1) and one new natural product, 3-epi-dihydroaltenuene A (2). The structures of the new metabolites were elucidated by comprehensive analysis of the spectroscopic data including (1D, 2D) NMR and HRESIMS, while the absolute configuration of 1 was determined by TDDFT-ECD computation. Altenuisol (5), 4-hydroxyalternariol-9-methyl ether (6), and alternariol (7) showed inhibitory activities against the tested bacteria with minimum inhibitory concentration values in the range of 86.7-364.7 μM. A preliminary structure-antibacterial activity relationship was discussed. In addition, compounds 2, 5 and 6 displayed promising antioxidant effects using DPPH and hydroxyl radical assays. The cytotoxicity of the isolated compounds was evaluated as well.

One bioactive compound, identified as alternariol 9-methyl ether, was isolated from the crude extract of the endophytic fungus Alternaria sp. Samif01 residing in the roots of Salvia miltiorrhiza Bunge. Alternariol 9-methyl ether was active against bacteria with minimum inhibitory concentration values ranging from 25 to 75μg/mL and median inhibitory concentration (IC50) values ranging from 16.00 to 38.27μg/mL. The IC50 value of alternariol 9-methyl ether against spore germination of Magnaporthe oryzae was 87.18μg/mL. Alternariol 9-methyl ether also showed antinematodal activity against Bursaphelenchus xylophilus and Caenorhabditis elegans with IC50 values of 98.17μg/mL and 74.62μg/mL, respectively. This work is the first report on alternariol 9-methyl ether and its biological activities from the endophytic fungus Alternaria sp. Samif01 derived from S. miltiorrhiza Bunge. The results indicate the potential of Alternaria sp. Samif01 as a source of alternariol 9-methyl ether and also support that alternariol 9-methyl ether is a natural compound with high potential bioactivity against microorganisms.