Isolation of Unstable Isomers of Lucilactaene and Evaluation of Anti-Inflammatory Activity of Secondary Metabolites Produced by the Endophytic Fungus Fusarium sp. QF001 from the Roots of Scutellaria baicalensis

Abstract

The filamentous fungal pathogen Fusarium sp. causes several crop diseases. Some Fusarium sp. are endophytes that produce diverse valuable bioactive secondary metabolites. Here, extensive chemical investigation of the endophytic fungus, Fusarium sp. QF001, isolated from the inner rotten part of old roots of Scutellariae baicalensis resulted in the isolation of two new photosensitive geometrical isomers of lucilactaene (compounds 2 and 3) along with lucilactaene (6) and six other known compounds (fusarubin (1), (+)-solaniol (4), javanicin (5), 9-desmethylherbarine (7), NG391 (8) and NG393 (9)). Newly isolated isomers and lucilactaene were unstable under light at room temperature and tended to be a mixture in equilibrium state when exposed to a polar protic solvent during reversed phase chromatography. Normal phase chromatography under dim light conditions with an aprotic mobile phase led to the successful isolation of the relatively unstable isomers 2 and 3. Their structures were elucidated as 8(Z)-lucilactaene (2) and 4(Z)-lucilactaene (3) based on spectroscopic data. The absolute configuration of 4 was speculated to be R by computer-assisted specific rotation analysis. The isolated compounds could inhibit NO production and suppress pro-inflammatory cytokines expression in LPS-stimulated macrophage cells. These properties of the isolated compounds indicate their potential use as anti-inflammatory drugs.

Dihydrolucilactaene, a Potent Antimalarial Compound from Fusarium sp. RK97-94

“…RK97-94 culture revealed the presence of two additional unknown peaks, 2 and 3 , that overlapped with NG391/393 peaks in UPLC analysis (Figure S4). Peak 2 exhibited a UV max at 368 nm, as well as [M – H] − 402 m / z and [M + H] + 404 m / z in ESI-MS analysis, suggesting a molecular weight of 403 Da, which has never been reported for lucilactaene analogues. , Peak 3 displayed a similar mass of NGs in ESI-MS ([M – H] − 416 m / z ) but with a different retention time (Figure S4) and different UV max (360 nm) . A literature and database search suggested a possible known hydroxylated lucilactaene derivative …”

“…To this end, we proposed a reduction of the carbonyl group at C-12 to its corresponding alcohol. To verify this, compound 1 was subjected to 1D- and 2D-NMR spectroscopy (Table , Figures S7–S13), and the results were compared with previously reported data for NG391/393 …”

“…Lucilactaene-like compounds are characterized by a pentaene skeleton known for its instability . Thus, all purification steps for 1 – 3 were conducted away from light, as much as possible, by collecting fractions in opaque, tightly closed vials dipped in ice to minimize the instability of these compounds due to light, high temperature, or atmospheric oxygen.…”

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

“…Maharjan et al [134] reported isolation of nine compounds including quinones, fusarubin, ( +)-solaniol, javanicin, 9-desmethylherbarine, and pyrrole analogs; isomers of lucilactaene (59,60,61), (62), and ( 63) from roots of Scutellariae baicalensis. These isolated compounds showed potential anti-inflammatory activity by inhibiting NO production and pro-inflammatory cytokines in LPSinduced RAW 264.7 macrophage cells.…”

An Active Compound From Pseudomonas aeruginosa B27

“…The significance of natural compounds extracted from microorganisms has been shown in nutrition, agriculture, and healthcare sciences. 1 Numerous studies have shown that microorganisms can produce many novel metabolites, such as steroids, terpenoids, flavonoids, and alkaloids, which have conspicuous antitumor, 2,3 anti-microorganism, 4 anti-inflammatory, 5 antioxidative, 6 and sugar-reducing 7 activities. Microbial metabolites have been used extensively in medicine.…”