Canthinone alkaloids are novel protein tyrosine phosphatase 1B inhibitors

Asperentin B, a New Inhibitor of the Protein Tyrosine Phosphatase 1B

“…Inhibitors of PTP1B can reduce the resistance to insulin and due to enhanced insulin signaling increase the insulin-stimulated glucose uptake. Therefore, PTP1B inhibitors could be used as pharmaceuticals for the treatment of type 2 diabetes and obesity [8,18,19,20]. Metabolites belonging to a broad spectrum of compound classes—including terpenoids, phenolic compounds, alkaloids, as well as semi-synthetic compounds and derivatives thereof, i.e., kinsensoide, lobaric acid, and oleanolic acid—have been patented as promising PTP1B inhibitors [21].…”

“…The semi-synthetic inhibitors were more effective with IC 50 values mostly in the range of 0.1 μM to 12 μM. In addition, canthinone alkaloids exhibited IC 50 values in the range of 20 μM to 29 μM and (R)-4-Hydroxy-5-(hydroxymethyl)-3-(1-oxohexadecyl)-2(5H)-furanone (RK-682) inhibited the PTP1B with an IC 50 value of 4.5 μM [20]. In this study, an IC 50 value of 2 μM was observed for asperentin B ( 1 ).…”

Protein tyrosine phosphatase 1B inhibitory activity of alkaloids from Rhizoma Coptidis and their molecular docking studies

“…In comparison with the calculated binding energy of alkaloid 1 (Autodock 4.0 ¼-7.2 and Fred 2.0 ¼ À67.3 kcal/mol), alkaloid 2 (Autodock 4.0 ¼ À6.9 and Fred 2.0 ¼ À59.6 kcal/mol) and alkaloid 4 (Autodock 4.0 ¼ À7.7 and Fred 2.0 ¼ À64.3 kcal/mol), alkaloids containing dioxymethylene and dimethoxy groups substitutions greatly depressed the binding energy. Recently, Sasaki et al (2015) and Jung et al (2013) also reported that presence or lack of functional groups and its substitutions greatly affected the inhibition mode and binding energy, which is made clear by the fact that alkaloids 1 and 2 are similar type of inhibition but lack of functional groups greatly affected the inhibition mode and binding energy of alkaloid 4. Therefore, alkaloids 1 and 2 were stably posed in similar pocket/catalytic domains of PTP1B residues and alkaloid 4 showed different catalytic domains of PTP1B residues in Fig.…”

Determination of the absolute configuration of picrasidine Y, a naturally occurring β-carboline alkaloid

“…Canthin-5,6-dione derivatives represent a major group of alkaloids found in P. quassioides and have been reported to show the potent anticancer cytotoxicity and PTP1B inhibitory activity. 18,19 Using the synthetic method described here, it may be possible to synthesize chemical derivatives with longer alkyl chains or other substituting groups after constructing the canthin-5,6-dione backbone.…”

“…In addition to limonoids, a large number of b-carboline and canthinone alkaloids have been isolated from these plants. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Furthermore, these alkaloids have been reported to have a variety of biological activities, including PTP1B-inhibition, anti-inflammatory activity, cAMP-phosphodiesterase inhibition, and cytotoxicity. 6,14,[17][18][19] Picrasidine Y (1) isolated from P. quassioides is a b-carboline alkaloid, and the absolute configuration of the propionic acid side chain at position 1 of the backbone structure has not been determined (Fig.…”