Cytotoxic Metabolites from the Fungal Endophyte Alternaria sp. and Their Subsequent Detection in Its Host Plant Polygonum senegalense

Abstract

From the Egyptian medicinal plant Polygonum senegalense the fungal endophyte Alternaria sp. was isolated. Extracts of the fungus grown either in liquid culture or on solid rice media exhibited cytotoxic activity when tested in vitro against L5178Y cells. Chromatographic separation of the extracts yielded 15 natural products, out of which seven were new compounds, with both fungal extracts differing considerably with regard to their secondary metabolites. Compounds 1, 2, 3, 6, and 7 showed cytotoxic activity with EC 50 values ranging from 1.7 to 7.8 microg/mL. When analyzed in vitro for their inhibitory potential against 24 different protein kinases, compounds 1- 3, 5- 8, and 15 inhibited several of these enzymes (IC 50 values 0.22-9.8 microg/mL). Interestingly, compounds 1, 3, and 6 were also identified as constituents of an extract derived from healthy leaves of the host plant P. senegalense, thereby indicating that the production of natural products by the endophyte proceeds also under in situ conditions within the plant host.

New Austalides from the Sponge‐Associated Fungus Aspergillus sp.

“…[44] Only compound 11, previously reported to have smooth and cardinal muscle contractive activity when tested on guinea pigs, [33] exhibited pronounced cytotoxicity, with an IC 50 value of 0.2 μm. Compound 8 was reported to selectively block translation in HeLa cells with no effect on yeast.…”

Total Synthesis of Neoaltenuene

“…[16] The synthesis of boronate A has been published previously [14] and an approach to halide B should be possible starting from tartaric acid (9) or, alternatively, quinic acid (10, Scheme 1). The use of tartaric acid would have the advantage of both enantiomers being available as starting materials.…”

“…[3] Numerous investigations have been published on alternariol (1) and alternariol 9-methyl ether (2), [4] and total syntheses have been reported for these compounds. [5] Much less is known about minor Alternaria toxins such as altenuene (3), [1b,6-9] isoaltenuene (4), [8,10] neoaltenuene (5), [11] 5Ј-epialtenuene (6), [11][12][13] or the recently isolated 4Ј-epialtenuene (7), [9,13] which have been isolated from infested fruits in submilligram amounts. Although we have previously published the total syntheses of altenuene (3) and isoaltenuene (4), [14] neither report details biological data [15] or their absolute configurations, nor have the total syntheses of the compounds 5-7 been published.…”

Induced production of mycotoxins in an endophytic fungus from the medicinal plant Datura stramonium L.

“…2). 21 Finally, the appearance of the 1 H signal at C-2 0 and the carboxyl group at C-7, and the molecular formula of 4 (C 15 H 14 O 6 ) established that 4 was a biphenyl, altenusin, which has also been isolated from Alternaria fungus (Fig. 2).…”