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Six new polyoxygenated seco-cyclohexenes, artahongkongenes A–F ( 1–6 ), together with six known analogues ( 7–12 ) were isolated from the stems and leaves of Artabotrys hongkongensis . Their structures were elucidated by extensive spectroscopic methods. All new compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro . New seco-cyclohexenes 1–6 showed significant inhibitory effects against various human cancer cell lines with IC 50 values ranging from 0.26 to 16.58 μM. [ABSTRACT FROM AUTHOR]

A hierarchical virtual screening was applied to identify natural products as new prototypes of PTP1B inhibitors. Ten compounds exhibited IC 50 values at the micromolar level, and nine of them demonstrated evident selectivity to PTP1B over four other PTPs. • Natural hits were identified as PTP1B inhibitors by virtual screening. • Ten hits demonstrated excellent potency with IC 50 at micromolar level against PTP1B. • Several hits showed evident selectivity to PTP1B over four other PTPs, including TCPTP. • A linear furancoumarin skeleton was recognized as a new prototype for PTP1B inhibitors. Protein tyrosine phosphatase 1B (PTP1B) is emerging as a promising yet challenging target for drug discovery. To identify natural products as new prototypes for PTP1B inhibitors, we employed a hierarchical protocol combining ligand-based and structure-based approaches for virtual screening against natural product libraries. Twenty-six compounds were prioritized for enzymatic evaluation against PTP1B, and ten of them were recognized as potent PTP1B inhibitors with IC 50 values at the micromolar level. Notably, nine compounds demonstrated evident selectivity to PTP1B over four other PTPs, including the most homologous T -cell protein tyrosine phosphatase (TCPTP). The results implicated that the structural uniqueness of the natural products might be a potential solution to the selectivity issue associated with the target PTP1B. [ABSTRACT FROM AUTHOR]

[Display omitted] • 27 PAB derivatives were designed and synthesized for evaluation against four cancer cell lines. • Compound D3 had a superior safety profile with a selectivity index (SI) of 20.38 compared to PAB's SI of 0.95. • Compound D3 suppressed cell proliferation, reduced colony formation, induced apoptosis, and arrested HCT-116 cells in specific phases. • In vivo experiments demonstrated low toxicity of compound D3 and its ability to suppress tumor growth in mice. Pseudolaric Acid B (PAB), a natural product with remarkable anti-tumor activity, is a starting point for new anticancer therapeutics. We designed and synthesized 27 PAB derivatives and evaluated their anti-proliferative activities against four cancer cell lines: MCF-7, HCT-116, HepG2, and A549. Compared with unmodified PAB, the PAB derivatives showed stronger anti-proliferative activity. The ability of compound D3 (IC 50 = 0.21 μM) to inhibit HCT-116 cells was approximately 5.3 times that of PAB (IC 50 = 1.11 μM) and the antiproliferative action was unrelated to cytotoxicity (SI=20.38), indicating its superior safety profile (PAB; SI=0.95). Compound D3 effectively suppressed the EdU-positive rate and reduced colony formation, arrested HCT-116 cells in the S and G2/M phases and induced apoptosis. In vivo experiments further demonstrated low toxicity of compound D3 while suppressing tumor growth in mice. In summary, given its strong anti-proliferative effect and relative safety, further development of compound D3 is warranted. [ABSTRACT FROM AUTHOR]

Two novel γ -lactone derivatives, trigoheterophines A ( 1 ) and B ( 2 ), together with four known furan derivatives ( 3 – 6 ), were isolated from the stems and leaves of Trigonostemon heterophyllus . The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparing with the data reported in literature. Among them, trigoheterophines A ( 1 ) and B ( 2 ) represent an unusual type of γ -lactone derivatives, possessing 21 carbon atoms on the carbon skeleton, and known compouds ( 3 – 6 ) are rare furan derivatives in the plant kingdom with diverse long-chain hydrocarbyl groups as substituents at C-4. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro . Compounds 1 – 6 showed significant antiproliferative effects against various human cancer cell lines with IC 50 values ranging from 0.28 to 12.06 μM. These findings suggest that the discoveries of these novel γ -lactone derivatives and furan derivatives with significant antiproliferative activities isolated from T. heterophyllus could be of great importance to the development of new anticancer agents. [ABSTRACT FROM AUTHOR]

[Display omitted] PTP1B plays an important role as a key negative regulator of tyrosine phosphorylation associated with insulin receptor signaling in the therapy for diabetes and obesity. In this study, the anti-diabetic activity of dianthrone derivatives from Polygonum multiflorum Thunb., as well as the structure–activity relationships, mechanism, and molecular docking were explored. Among these analogs, trans -emodin dianthrone (compound 1) enhances insulin sensitivity by upregulating the insulin signaling pathway in HepG2 cells and displays considerable anti-diabetic activity in db/db mice. By using photoaffinity labeling and mass spectrometry-based proteomics, we discovered that trans -emodin dianthrone (compound 1) may bind to PTP1B allosteric pocket at helix α6/α7, which provides fresh insight into the identification of novel anti-diabetic agents. [ABSTRACT FROM AUTHOR]

[Display omitted] • Six new oligostilbenes obtained from the stems of Caragana sinica. • Natural tetrastilbenes were determined as absolute configuration for the first time. • Obvious inhibition of α -glucosidase in vitro with IC 50 values of 0.1 ∼ 0.4 μ M. • Leachianol (7) showed significant inhibition (88.8%, 10 μ M) of protein tyrosine phosphatase (PTP1B) with IC 50 value of 1.1 μ M in vitro. Six new oligostilbenes, carastilphenols A-E (1 – 5) and (–)-hopeachinol B (6), with three reported oligostilbenes were obtained from the stems of Caragana sinica. The structures of compounds 1 – 6 were determined by comprehensive spectroscopy analysis, and their absolute configurations were determined by electronic circular dichroism calculations. Thus, natural tetrastilbenes were determined as absolute configuration for the first time. Also, we did several pharmacological essays. In the antiviral tests, compounds 2 , 4 and 6 showed moderate anti-coxsackie virus B3 type (CVB3) effect on Vero cells activities in vitro with IC 50 values of 19.2 ∼ 69.3 μ M; and compounds 3 and 4 showed different levels of anti-respiratory syncytial virus (RSV) effect on Hep2 cells activities in vitro with IC 50 values of 23.1 and 33.3 μ M, respectively. As for hypoglycemic activity, compounds 6 – 9 (10 μ M) showed the inhibition of α -glucosidase in vitro with IC 50 values of 0.1 ∼ 0.4 μ M; and compound 7 showed significant inhibition (88.8%, 10 μ M) of protein tyrosine phosphatase 1B (PTP1B) with IC 50 value of 1.1 μ M in vitro. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nine undescribed monoterpene phenol dimers bisbakuchiols D-L (1 – 9) were isolated from the fruits of Psoralea corylifolia L. • A single crystal of compound 1 was obtained, and the absolute configurations of 1 was established by X-ray diffraction. • Compounds 5 and 9 exhibited significant PTP1B inhibitory activities with IC 50 values of 0.69 and 0.73 μ M. • A Molecular docking simulation of PTP1B and compounds 5 and 9 exhibited that these active compounds possess low binding affinities ranging from −6.9 to −7.1 kcal/mol. Nine undescribed monoterpene phenol dimers, bisbakuchiols D-L (1 – 9), were isolated from the fruits of Psoralea corylifolia L. Their structures were elucidated based on extensive spectral analysis. The absolute configurations of 1 – 9 were specified by experimental and quantum chemical calculations of ECD spectra, and that of 1 was further established by X-ray diffraction analysis using Cu Kα radiation. Bisbakuchiols (1 – 4) were composed of two bakuchiols, one of which was cyclized via a C-7′/ C-12′ single bond to form a six-member ring, and connect to each other by C–4–O–C–13 ' bonds. Bisbakuchiols (7 – 9) had a pyran ring by linkage of C–8–O–C–12. In the enzyme assay, compounds 5 and 9 exhibited significant PTP1B inhibitory activities with IC 50 values of 0.69 and 0.73 μ M, and compounds 1 and 3 showed moderate PTP1B inhibitory activities. Furthermore, a molecular docking simulation of PTP1B and active compounds 5 and 9 showed that these active compounds possess low binding affinities ranging from −6.9 to −7.1 kcal/mol. [ABSTRACT FROM AUTHOR]