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

ABSTRACT 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.