Protein Tyrosine Phosphatase 1B Inhibitors from the Stems of Akebia quinata

Abstract

PTP1B deficiency in mouse mammary tumor virus (MMTV)-NeuNT transgenic mice inhibited the onset of MMTV-NeuNT-evoked breast cancer, while its overexpression was observed in breast cancer. Thus, PTP1B inhibitors are considered chemopreventative agents for breast cancer. As part of our program to find PTP1B inhibitors, one new diterpene glycoside (1) and 13 known compounds (2-14) were isolated from the methanol extract of the stems of Akebia quinata. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR and MS. Compounds 2, 3, 6, 8 and 11 showed significant inhibitory effects on the PTP1B enzyme, with IC 50 values ranging from 4.08 ± 1.09 to 21.80 ± 4.74 µM. PTP1B inhibitors also had concentration-dependent cytotoxic effects on breast cancer cell lines, such as MCF7, MDA-MB-231 and tamoxifen-resistant MCF7 (MCF7/TAMR) (IC 50 values ranging from 0.84 ± 0.04 to 7.91 ± 0.39 µM). These results indicate that compounds 6 and 8 from Akebia quinata may be lead compounds acting as anti-breast cancer agents.

Anti-Inflammatory Triterpenoids from the Caulophyllum robustum Maximin LPS-Stimulated RAW264.7 Cells

“…The structures of the new compounds ( 1 – 3 ) were elucidated on the basis of extensive NMR spectroscopic analysis, including a series of 2D-NMR experiments ( Figure 2 ) (HSQC, HMBC), and mass spectrometry data. The known compounds ( 4 – 10 ) were identified by comparison of their experimental spectral data with literature data [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ].…”

Cytotoxic and Anti-inflammatory Terpenoids from the Whole Plant of Vaccinium emarginatum

“…Its cytotoxicity was associated with the EtOAc-soluble fraction, which more potently inhibited PC-3 proliferation with 35.1 % (± 1.2) inhibition at the same concentration. The phytochemical investigation of the EtOAc-soluble fraction of the V. emarginatum MeOH extract yielded two new Δ 12 ursenetype triterpenoid coumaroyl esters (1 and 2), one new Δ 12 isopimarane-type diterpenoid glycoside (20), and two new irido-δ-lactone-type iridoids (21 and 22), together with 17 known pentacyclic triterpenoids (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)) (▶ Fig. 1).…”

“…1). The known compounds were identified as 3β-O-(E)-feruloyl-19α-hydroxy-urs-12-ene-28-oic acid (3) [10], 3β-O-(Z)-feruloyl-19α-hydroxy-urs-12-ene-28-oic acid (4) [10], 3β-O-(E)-feruloyl oleanolic acid (5) [11], 3β-O-(E)-feruloyl ursolic acid (6) [11], ursolic acid (7) [12], pomolic acid (8) [13], rotundic acid (9) [13], 2α,3α,23-trihydroxyurs-12-en-28-oic acid (10) [14], euscaphic acid (11) [15], myrianthic acid (12) [15], rotundanonic (13) [16], 3-oxo-19,23,24-trihydroxyurs-12-en-28-oic acid (14) [17], maslinic acid (15) [18], arjunolic acid (16) [19], 2α,3α,23-trihydroxyolean-12-en-28-oic acid (17) [20], friedelin (18) [21], and epi-friedelinol (19) [21] based on their spectroscopic data, which were identical to literature values. The structures of compounds 1, 2, and 20-22 were elucidated by detailed analysis of standard spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HRESIMS), IR spectroscopy, and 1D and 2D NMR and by comparison with the spectroscopic data of known analogs.…”

Synthesis of small peptide compounds, molecular docking, and inhibitory activity evaluation against phosphatases PTP1B and SHP2

“…Because PTP1B and SHP2 are associated with multiple cancer-related diseases, as well as SHP2 is a potential immunomodulator, which alters autoimmunity and related immunopathology, controlling PTP1B and SHP2 activities is of significant therapeutic interest 30,31. Studies have indicated that some natural diterpenes reveal significant inhibitory effects on the PTP1B enzyme and are considered an anti-breast cancer agents 32…”