Kuwanon X

Phytochemical Profiling of Mulberry Diels-Alder Adducts as Selective Butyrylcholinesterase Inhibitors: In Vitro Activity, Molecular Docking, and Molecular Dynamics Simulation.[Pubmed:42197128]

Molecules. 2026 May 8;31(10):1574.

Alzheimer's disease (AD) is a common neurodegenerative disorder linked to cholinergic dysfunction, with butyrylcholinesterase (BChE) being a key therapeutic target for moderate-severe AD. Cortex Mori Radicis, a traditional Chinese medicinal herb, is rich in Diels-Alder adducts with potential neuroprotective effects; here, eighteen Diels-Alder adducts (four new: morusalbanol B-E, 1-4) were isolated and identified from its 80% ethanol extract. Their cholinesterase inhibitory activities were assessed via Ellman's method, with enzyme kinetics and molecular docking performed for active compounds. Most compounds showed selective BChE inhibition, with Kuwanon X (14) being the most potent (IC(50) = 2.3 muM). morusalbanol B (1), cathayanon A (8), and kuwanon G (12) acted as noncompetitive inhibitors, while Morusalbanol C (2) and Kuwanon X (14) were mixed competitive inhibitors. Molecular docking suggested that potent inhibitors occupied the BChE active pocket via hydrogen bonds, pi-pi stacking, and hydrophobic interactions with Trp82, His438, and Phe329. MD simulations and MM-GBSA binding free energy analysis further verified that all three representative complexes (1, 8, and 14) achieved favorable thermodynamic and structural stability, with binding driven primarily by van der Waals forces. Residue decomposition revealed that Trp82 and Phe329 served as core binding hotspots for all tested inhibitors. Structure-activity analysis indicated that a cis-trans methylcyclohexene configuration, shorter aliphatic ester chains, and more prenyl groups enhanced BChE inhibition. This study provides new lead compounds and a systematic molecular mechanism basis for developing novel anti-AD BChE inhibitors from natural products.

Anti-HSV Activity of Kuwanon X from Mulberry Leaves with Genes Expression Inhibitory and HSV-1 Induced NF-kappaB Deactivated Properties.[Pubmed:27725444]

Biol Pharm Bull. 2016;39(10):1667-1674.

Six stilbene derivatives isolated from Mulberry leaves including Kuwanon X, Mulberrofuran C, Mulberrofuran G, Moracin C, Moracin M 3'-O-b-glucopyranoside and Moracin M were found to have antiviral effects against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) at different potencies except for Mulberrofuran G. Kuwanon X exhibited the greatest activity against HSV-1 15577 and clinical strains and HSV-2 strain 333 with IC(50) values of 2.2, 1.5 and 2.5 microg/mL, respectively. Further study revealed that Kuwanon X did not inactivate cell-free HSV-1 particles, but inhibited cellular adsorption and penetration of HSV-1 viral particles. Following viral penetration, Kuwanon X reduced the expression of HSV-1 IE and L genes, and decreased the synthesis of HSV-1 DNA. Furthermore, it was demonstrated that Kuwanon X inhibited the HSV-1-induced nuclear factor (NF)-kappaB activation through blocking the nuclear translocation and DNA binding of NF-kappaB. These results suggest that Kuwanon X exerts anti-HSV activity through multiple modes and could be a potential candidate for the therapy of HSV infection.

Enantioselective Total Syntheses of Kuwanon X, Kuwanon Y, and Kuwanol A.[Pubmed:26756182]

Org Lett. 2016 Feb 5;18(3):360-3.

The first enantioselective total syntheses of (-)-Kuwanon X, (+)-kuwanon Y, and (+)-kuwanol A have been accomplished by using asymmetric Diels-Alder cycloaddition promoted by chiral VANOL or VAPOL/boron Lewis acid. The biosynthesis-inspired asymmetric Diels-Alder cycloaddition shows high exo selectivity (exo/endo = 13/1), which was unprecedented in the previous total syntheses of related prenylflavonoid Diels-Alder natural products. An acid catalyzed intramolecular ketalization process enabled a biomimetic transformation to construct the polycyclic skeleton of kuwanol A efficiently.

Fluorescence resonance energy transfer assay for high-throughput screening of ADAMTS1 inhibitors.[Pubmed:22186957]

Molecules. 2011 Dec 20;16(12):10709-21.

A disintegrin and metalloprotease with thrombospondin type I motifs-1 (ADAMTS1) plays a crucial role in inflammatory joint diseases and its inhibitors are potential candidates for anti-arthritis drugs. For the purposes of drug discovery, we reported the development and validation of fluorescence resonance energy transfer (FRET) assay for high-throughput screening (HTS) of the ADAMTS1 inhibitors. A FRET substrate was designed for a quantitative assay of ADAMTS1 activity and enzyme kinetics studies. The assay was developed into a 50-microL, 384-well assay format for high throughput screening of ADAMTS1 inhibitors with an overall Z' factor of 0.89. ADAMTS1 inhibitors were screened against a diverse library of 40,960 total compounds with the established HTS system. Four structurally related hits, naturally occurring compounds, kuwanon P, Kuwanon X, albafuran C and mulberrofuran J, extracted from the Chinese herb Morus alba L., were identified for further investigation. The results suggest that this FRET assay is an excellent tool, not only for measurement of ADAMTS1 activity but also for discovery of novel ADAMTS1 inhibitors with HTS.

[Study on Diels-Alder type adducts from stem barks of Morus yunanensis].[Pubmed:19445150]

Zhongguo Zhong Yao Za Zhi. 2009 Feb;34(3):286-90.

OBJECTIVE: To isolate and identify the Diels-Alder type adducts from stem barks of Morus yunanensis. METHOD: The compounds were isolated and purified by silicagel, Sephadex LH-20 and RP-18 colum chromatography. Their chemical structures were elucidated on the basis ofphysicochemical properties and spectral data. RESULT: Nine compounds were isolated and identified as: kuwanon G (1), sanggenol M (2), mulberrofuran J (3), guangsangon B (4), resveratrol (5), Kuwanon X (6), kuwanon P (7), mulberrofuran O (8), mulberrofuran Q (9). CONCLUSION: All the compounds are isolated from the plant for the first time, and compounds 4, 5 have anti-inflammation activities with inhibitory ratios of 57.3%, 50.5% respectively at a concentration of 10 microg mL(-1).

Bioactive diels-alder type adducts from the stem bark of Morus macroura.[Pubmed:15368673]

Planta Med. 2004 Aug;70(8):758-63.

Five new compounds, named guangsangons A (1), B (5), C (6), D (7), and E (8), along with four known compounds, albafuran C (2), Kuwanon X (3), kuwanon P (4), and kuwanon Y (9) were isolated from Morus macroura Miq.. Their structures were determined by means of spectroscopic analyses and chemical methods. These compounds were regarded biogenetically as Diels-Al-der type adducts, and 1H-NMR variable temperature experience suggested that they all existed as an equilibrium mixture of conformational isomers in solution. Compounds 1-3 and 5-9 showed good anti-oxidation activity, with the inhibitory rate of malondialdehyde being from 90.1% to 102.7% at a concentration of 10(-4) mol/L and from 70.9% to 88.1% at a concentration of 10(-5) mol/L. Compounds 1, 5, and 7 showed anti-inflammation activity, with the inhibitory rates of release of lysosome enzyme from polymorphonuclear leukocytes of rats being 19.0% (P > 0.05), 57.3% (P < 0.001) and 24.3% (P < 0.05) at concentrations of 10(-5) mol/L, respectively.

Kuwanon X (CAS 96819-92-0) is a natural product offered by BioCrick for research applications. Customers can buy or order Kuwanon X from BioCrick, a supplier and manufacturer of research chemicals, with product specifications, purity, packaging, and pricing information available upon request.