An Oxazole Alkaloid, Terpenoids, and Cyclodipeptides With Cytotoxic and Nitric Oxide Inhibitory Effects From a Mangrove-Derived Fungus Trichoderma sp. GXT-22.1

Chemical investigation of the mangrove-derived fungus Trichoderma sp. GXT-22.1 led to the isolation and identification of 10 secondary metabolites, including one new compound, 5′-(4-methoxyphenyl)-1′,3′-oxazole (1), one new natural compound, (E)-6,10-dimethyl-5-undecene-2,9,10-triol (2), along with eight known compounds, tricholumin A (3), harzianol J (4), cyclonerodiol (5), 10,11-dihydro-11-hydroxycyclonerodiol (6), cyclonerodiol B (7), epicyclonerodiol oxide (8), cyclo(Val-Pro) (9), and cyclo-(4-hydroxyprolinyl-leucine) (10). The structural feature of oxazole in 1 was unusually found among the fungal metabolites. Compounds 1 and 4 exhibited weak cytotoxicity toward HepG2 and MCF-7 human carcinoma cell lines at the concentration of 100 µM, with induction of 41.5 ± 3.0% and 39.3 ± 2.3% cell death, respectively. Compounds 1−5, 8, and 10 showed their inhibitory effect against nitric oxide (NO) overproduction in lipopolysaccharide-stimulated RAW264.7 cells, with half inhibition concentration values ranging from 37.5 ± 2.6 to 86.5 ± 5.1 µM. Molecular docking simulation suggested that 1 inhibits NO overproduction via modulating the action of the inducible NO synthase protein.