Dimeric N-Acetyldopamine Derivatives Featuring a Seco-Benzene System from the Insects Aspongopus chinensis and Periostracum cicadae.

Aspongamide F (1), a novel N-acetyldopamine (NADA) dimer possessing a 6/6/6 ring system, and (±)-aspongamides G (2) and H (3), rare NADA derivatives with fragmented benzene rings, were isolated from Aspongopus chinensis. (±)-Cicadamides C (4) and D (5), the first 1,4-Benzodioxane NADA dimers featuring a seco-benzene system, and (±)-cicadamides E (6) and F (7), the NADA dimers derivatives, were isolated from Periostracum cicadae. The structures of all compounds were elucidated by spectroscopic analyses and computational methods. A plausible biosynthetic pathway for compounds 1-5 was proposed. The biological assay revealed that (+)-4 and (-)-4 exhibit renal protection in a dose-dependent manner.

Racemic norneolignans from the resin of Ferula sinkiangensis and their COX-2 inhibitory activity.

Five new norneolignans sinkianlignans G-K (1-5), one phenolic compound ferulagenol A (6) and seven known compounds (7-13) were isolated from Ferula sinkiangensis. All the norneolignans were racemic mixtures, and chiral HPLC was used to further separate them. Their structures were assigned, including absolute configurations, using spectroscopic and computational methods. Biological evaluation showed that compounds 1-9 had significant COX-2 inhibitory activity with IC50 values ranging from 3.00 µM to 23.19 µM.

Terminal Cyclohexane-Type Meroterpenoids from the Fruiting Bodies of Ganoderma cochlear.

Eleven new cyclohexane-type meroterpenoids (1, 3-5, 7, 8, 11-15) and four known similar meroterpenoids (2, 6, 9, and 10) were isolated from Ganoderma cochlear. Their structures and absolute configurations at stereogenic centers were elucidated by using HRESIMS, NMR spectroscopy and computational methods. In addition, the structure of the known meroterpenoid, cochlearol G (2), was revised, and the absolute configurations at the stereogenic centers of known meroterpenoids 9 and 10 were determined. All the isolated meroterpenoids were evaluated for their activities against renal fibrosis and triple negative breast cancer, and their insulin resistance. The results of the renal fibrosis study showed that meroterpenoid 11 inhibits over-expression of fibronectin, collagen I and α-SMA. Results of the wound healing study revealed that 4, 6 and 8 significantly inhibit migration of BT549 cells. Observations made in Western blotting experiments showed that 6 decreases the levels of TWIST1 and ZEB1, and increases the level of E-cadherin. Finally, meroterpenoids 7, 9, 11, and 15 significantly up-regulate p-AMPK protein expression in normal L6 myotubes cells.

Gancochlearols E - I, meroterpenoids from Ganoderma cochlear against COX-2 and triple negative breast cancer cells and the absolute configuration assignment of ganomycin K.

Five new meroterpenoids, gancochlearols E - I (1, 3-6), and one compound ganomycin K (2) were isolated from the fruiting bodies of G. cochlear. Their structures were assigned by 1D and 2D NMR, MS, and CD analysis. Rh2(OCOCF3)4-induced ECD method was used to clarify the absolute configuration of secondary alcohol in 1 and 2. Biochemical evaluation showed that all the isolates significantly inhibit COX-2 enzyme in vitro with the IC50 values range from 1.03 µM to 2.71 µM. Further cellular assay revealed that (+)-3 and (-)-6 could suppress metastatic phenotype of triple-negative breast cancer (TNBC) cells via impeding the epithelial-mesenchymal transition (EMT).

Periplanetols A-F, phenolic compounds from Periplaneta americana with potent COX-2 inhibitory activity.

Six new compounds, periplanetols A - F (1-4, 6 and 7), a compound isolated from natural origin for the first time (5), and nine known ones (8-16) were isolated from the 70% ethanol extract of the whole bodies of Periplaneta americana. Their structures including absolute configurations were unambiguously identified by comprehensive spectroscopic analyses and computational methods. Biological evaluation toward COX-2 inhibition revealed that compounds 1, 2, and 10 could inhibit COX-2 activity with the IC50 values of 768.0 nM, 617.7 nM, and 599.5 nM respectively, indicating their potential in developping novel agents against inflammation related disorders.

Racemic xanthine and dihydroxydopamine conjugates from Cyclopelta parva and their COX-2 inhibitory activity.

Seven new compounds including three pairs of enantiomeric xanthine analogues (1-3), a pair of enantiomeric hypoxanthine analogue (4), and three pairs of enantiomeric N-acetyldopamine dimers (6-8), together with a known one (5) were isolated from the insect Cyclopelta parva. Their structures including absolute configurations were assigned by using spectroscopic and computational methods. Chiral HPLC was used to separate racemic 1-8. Biological evaluation found that 6b and 7a are potent COX-2 inhibitory agents with IC50 values at 385.2 nM and 868.8 nM respectively.

Ganoderma cochlear Metabolites as Probes to Identify a COX-2 Active Site and as in Vitro and in Vivo Anti-Inflammatory Agents.

(±)-Dispirocochlearoids A-C (1-3), meroterpenoids with a 6/6/5/6/6/6 ring system, were isolated from Ganoderma cochlear. 1-3 are selective COX-2 inhibitors with an IC50 value of (-)-2 at 386 nM. Site-directed mutagenesis identified His351 as a COX-2 active site. In vivo anti-inflammatory activities of (-)-2 were performed against acute lung injury in mice.

(+/-)-Lucidumone, a COX-2 Inhibitory Caged Fungal Meroterpenoid from Ganoderma lucidum.

(±)-Lucidumone (1), an enantiomeric meroterpenoid possessing an unprecedented skeleton comprising a fused 6/5/6/6/5 polycyclic system, was isolated from Ganoderma lucidum and structurally identified. The absolute configuration of (-)-1 was assigned by single-crystal X-ray crystallography. A plausible biosynthetic pathway for 1 is proposed. A chemical biology approach reveals that (-)-1 selectively inhibits COX-2 by directly binding with an amino acid residue of Tyr385, representing a new structure scaffold of COX-2 inhibitors.