Duc Hung Nguyen

Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their protein tyrosine phosphatase and acetylcholinesterase inhibitory activities

A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and another flavone glycoside with spectroscopic data reported for the first time, kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1→6)]-β-d-glucoside (3), along with 16 known compounds were isolated from the aerial parts of Agrimonia pilosa Ledeb. These compounds were evaluated for PTP1B inhibitory activity. Among them, compounds 9 and 18 displayed potential inhibitory activity against PTP1B with IC50 values of 7.14±1.75 and 7.73±0.24μM, respectively. In addition, compound 1 showed significant inhibitory effect with an IC50 value of 17.03±0.09μM. Furthermore, these compounds were tested in AChE inhibitory assays. Most of them were found to have moderate inhibitory effects, with IC50 values ranging from 60.20±1.09 to 92.85±1.12μM. Except compounds 3, 8, and 18 were inactive.

PTP1B inhibitors from Selaginella tamariscina (Beauv.) Spring and their kinetic properties and molecular docking simulation

Diabetes is one of the most popular worldwide diseases, regulated by the defects in insulin secretion, insulin action, or both. The overexpression of protein tyrosine phosphatase 1B (PTP1B) was found to down-regulate the insulin-receptor activation. PTP1B has been known as a strategy for the treatment of diabetes via the regulation of insulin signal transduction pathway. Herein, we investigated the PTP1B inhibitors isolated from natural sources. The chemical investigation of Selaginella tamariscina (Beauv.) Spring revealed seven unsaturated alkynyl phenols 1-7, four new selaginellins T-W 1-4 together with three known compounds 5-7 isolated from the aerial parts. The structures of the isolates were determined by spectroscopic techniques (1D/2D-NMR, MS, and CD). The inhibitory effects of these isolates on the PTP1B enzyme activity were investigated. Among them, compounds 2-7 significantly exhibited the inhibitory effects with the IC50 values ranging from 4.8 to 15.9μM. Compound 1 moderately displayed the inhibitory activity with an IC50 of 57.9μM. Furthermore, active compounds were discovered from their kinetic and molecular docking analysis. The results revealed that compounds 2 and 4-7 were mixed-competitive inhibitors, whereas compound 3 was a non-competitive inhibitor. This data confirm that these compounds exhibited potential inhibitory effect on the PTP1B enzyme activity.

Isolation of Lignan and Fatty Acid Derivatives from the Grains of Echinochloa utilis and Their Inhibition of Lipopolysaccharide-Induced Nitric Oxide Production in RAW 264.7 Cells

Two new fatty acid derivatives, echinochlorins A (8) and B (9) and a racemic lignan, (±)-anti-1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-acetoxypropen-1-yl]-2-methoxyphenoxy}propan-1,3-diol 3-acetate (1), were isolated from Echinochloa utilis grains, along with six known lignans (2-7) and two fatty acid derivatives (10, 11). Their structures were established by spectroscopic data analyses (IR, UV, HR-FABMS, GC-MS, and 1D and 2D NMR). The configuration of 1 was determined by Moshers method. Compound 5 displayed potential inhibitory activity on lipopolysaccharide-induced NO production in macrophage RAW 264.7 cells with an IC50 value of 4.8 ± 0.5 μM. These isolated compounds in crude EtOH extract were also quantitated by HPLC.

PTP1B inhibitory and cytotoxic activities of triterpenoids from the aerial parts of Agrimonia pilosa

Recently, PTP1B inhibitors have become the frontier as possible targeting for anti-cancer and anti-diabetic drugs. Twelve triterpenoids from the aerial parts of Agrimonia pilosa were investigated for PTP1B inhibitory and cytotoxic activities. In the results, compounds 3 (IC50 = 0.50 μM) and 7 (IC50 = 5.88 μM) were found to possess very powerful inhibitory activity against the PTP1B enzyme, comparable to the positive control ursolic acid (IC50 = 6.60 μM). In addition, compounds 1, 2, 4, and 10‒12 showed potent inhibitory effects against PTP1B, with an IC50 range of 13.48‒14.98 μM. In the kinetic assay of the PTP1B enzyme, compounds 1 and 2 were noncompetitive, whereas 7 and 11 showed a mixed type. In the docking analysis, the results showed that different residues of PTP1B interacted with twelve triterpenoids. Furthermore, compounds 6 (IC50 = 3.65 μM) and 12 (IC50 = 1.21 μM) displayed strong cytotoxic effects against the HeLa cell line. Compounds 2 (IC50 = 16.06 μM) and 4 (IC50 = 14.73 μM) showed moderate cytotoxic activities against the HeLa cell line. Compound 2 exhibited comprehensive cytotoxicity against the HL-60 (IC50 = 45.53 μM) and MCF-7 (IC50 = 34.21 μM) cell lines. These results support the use of triterpenoids in traditional medicine for prevention and treatment of diabetes and cancer.Recently, PTP1B inhibitors have become the frontier as possible targeting for anti-cancer and anti-diabetic drugs. Twelve triterpenoids from the aerial parts of Agrimonia pilosa were investigated for PTP1B inhibitory and cytotoxic activities. In the results, compounds 3 (IC50 = 0.50 μM) and 7 (IC50 = 5.88 μM) were found to possess very powerful inhibitory activity against the PTP1B enzyme, comparable to the positive control ursolic acid (IC50 = 6.60 μM). In addition, compounds 1, 2, 4, and 10‒12 showed potent inhibitory effects against PTP1B, with an IC50 range of 13.48‒14.98 μM. In the kinetic assay of the PTP1B enzyme, compounds 1 and 2 were noncompetitive, whereas 7 and 11 showed a mixed type. In the docking analysis, the results showed that different residues of PTP1B interacted with twelve triterpenoids. Furthermore, compounds 6 (IC50 = 3.65 μM) and 12 (IC50 = 1.21 μM) displayed strong cytotoxic effects against the HeLa cell line. Compounds 2 (IC50 = 16.06 μM) and 4 (IC50 = 14.73 μM) showed moderate cytotoxic activities against the HeLa cell line. Compound 2 exhibited comprehensive cytotoxicity against the HL-60 (IC50 = 45.53 μM) and MCF-7 (IC50 = 34.21 μM) cell lines. These results support the use of triterpenoids in traditional medicine for prevention and treatment of diabetes and cancer.

Six selaginellin derivatives with protein tyrosine phosphatase 1B inhibitory activity from Selaginella tamariscina

As part of an ongoing search for new PTP1B inhibitors from medicinal plants, the methanol extract of the aerial parts of Selaginella tamariscina was found to inhibit 70% PTP1B enzyme activity at a concentration of 30 µg/mL. Thus, bioassay-guided isolation of this active extract yielded six selaginellin derivatives (1-6), comprising four new compounds (selariscinas A˜D; 2˜6). These compounds were found to possess inhibitory effect on PTP1B enzyme activity with IC50 values ranging from 5.5 ± 0.1 to 21.6 ± 1.5µM. Furthermore, compound 2 which served as mixed-competitive inhibitor showed the greatest potency, with IC50 value of 5.5 ± 0.1µM, when compared with the positive control (ursolic acid, IC50= 3.4 ± 0.1). This result indicated the potential of these selaginellin derivatives as lead molecules for the development of antidiabetic agents and the beneficial use of S. tamariscina against hyperglycemia.