BMS-182123, a Fungal Metabolite that Inhibits the Production of TNF-.ALPHA. by Macrophages and Monocytes.

Abstract

A fungal metabolite, BMS-182123, which inhibited bacterial endotoxin-induced production of tumor necrosis factor (TNF-a) in murine macrophages and humanperipheral blood monocytes (in vitro), was isolated from the culture broth of Penicillium chrysogenumstrain V39673.The effective BMS-1 82123 concentration (IC50) resulting in 50% inhibition of lipopolysaccharide-induced TNF-a production in murine macrophages and humanmonocytes was 600 ng/ml and 4.0 jug/ml, respectively. BMS-182123 suppressed the lipopolysaccahride-induced TNF-a promoter activity and did not affect the stability of posttranscriptional mRNA. Addition of hydrophobic resin, Amberlite XAD-8(1 %), to the fermentation enhanced the production of BMS-182123by 5.5 fold. A total of 577mg pure BMS-182123 was recovered from a 250-liter fermentation supplemented with 1 %Amberlite XAD-8.

Sorbicillinoids from Fungi and Their Bioactivities

“…Trichodimerol (=MS-182123, 42) from Penicillium chrysogenum strain V39673 inhibited the production of tumor necrosis factor-α (TNF-α) by macrophages (IC 50 value of 200 ng/mL) and monocytes (IC 50 value of 200 ng/mL) [46]. Subsequently, trichodimerol was screened to show an inhibitory effect on lipopolysaccharide-induced eicosanoid secretion in THP-1 human monocytic cells [66].…”

“…[22] Bisvertinolone (34) Inhibitory effect on β-l,6-glucan biosynthesis [42] Isobisvertinol (38) Inhibitory effect on lipid droplet accumulation in mouse macrophages [40] Trichodimerol (42) Inhibitory effect on bacterial endotoxin-induced production of tumor necrosis factor (TNF-α) in murine macrophages and human peripheral blood monocytes [46] Inhibitory effect on lipopolysaccharide-induced eicosanoid secretion in THP-1 human monocytic cells [66] Suppression of the production of tumor necrosis factor-α and nitric oxide in LPS-stimulate RAW264.7 cells [50] Dihydrotrichodimerol (44) Activation of peroxisome proliferator-activated recptor γ (PPAR γ) with an ED 50 of 80 ng/mL [50] Suppression of the production of tumor necrosis factor-α and nitric oxide in LPS-stimulate RAW264.7 cells [50] Effect on feeding perference of the aphid [48] Bislongiquinolide (49) Effect on feeding perference of the aphid [48] Sorbiterrin A (79) Inhibitory effect on acetylcholinesterase activity with IC 50 value of 25 µg/mL [61] Note: "ED 50 " means the median effective dose. "IC 50 " means the median inhibitory concentration.…”

Fungal Metabolites, Sorbicillinoid Polyketides and Their Effects on the Activation of Peroxisome Proliferator-activated Receptor γ

“…The maximum activity of dihydrotrichodimerol (2) activating PPARg was about 75 % of rosiglitazone, a well-known selective PPARg agonist [22]. Trichodimerol (1) has been reported to inhibit 618 TNF-a production in LPS-stimulated RAW264.7 cells [11]. Therefore, we compared the effects of compounds 1 and 2 on the production of inflammatory mediators, TNF-a and nitric oxide (NO), in LPS-stimulated RAW264.7 cells.…”

Dihydrotrichodimerol and Tetrahydrotrichodimerol, Two New Bisorbicillinoids, from a Marine-derived Penicillium terrestre

“…The similarity of 1 and 2 in their CD spectra showed 2 possessed the same absolute stereochemistry as 1 (Fig. 1 13 C NMR data of 3, helped by the 2D-NMR experiments (HMQC and HMBC), enabled 3 to be identified as trichodimerol, which had been isolated from a few fungi [5,6,10].…”

“…Cell culture and bioassay procedures were the same as article [2]. Bisorbicillinoids had some intriguing biological activities [6,10,12]. In our search, they were found to be cytotoxic to cancer cell lines.…”