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Diabetes mellitus is the most serious and prevalent metabolic disorders worldwide, complications of which can decrease significantly the quality of life and contribute to premature death. Resistance to insulin is a predominant pathophysiological factor of Type 2 diabetes (T2D). Protein tyrosine phosphatase 1B (PTP1B) is an important negative factor of insulin signal and a potent therapeutic target in T2D patients. This review highlights recent advances (2012-2015) in research related to the role of PTP1B in signal transduction processes implicated in pathophysiology of T2D, and novel PTP1B inhibitors with an emphasis on their chemical structures and modes of action.

A new prenylated dihydrobenzofuran derivative (1), was isolated from the rhizomes of Atractylodes lancea DC (Asteraceae), along with ten known compounds, including atractylenolide II (2), phi-taraxasteryl acetate (3), taraxerol acetate (4), beta-sitosterol (5), stigmasterol (6), beta-eudesmol (7), atractylenolide III (8), atractylenolide IV (9), daucosterol (10), and stigmasterol 3-O-beta-D-glucopyranoside (11). The structure of the new compound (1) was elucidated as trans-2-hydroxyisoxypropyl-3-hydroxy-7-isopentene-2,3-dihydrobenzofuran-5-carboxylic acid by the combination of 1D, 2D NMR analysis and mass spectrometry, and it was the first reported 2,3-dihydrobenzofuran derivative having a carboxyl residue at C-5 and an isopentene moiety at C-7 contemporaneously. In addition, compound 1 exhibited significant cytotoxicity against cancer cell lines HCT-116 and MKN-45.

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Luteolin has been shown to have a strong anticancer effect on various cancer models via programmed cell death (apoptosis). However, the fundamental mechanisms of these effects are still unclear. In the present study, we examined the question of whether or not luteolin can inhibit proliferation of pancreatic carcinoma cells, via apoptosis. We used three human pancreatic carcinoma cell lines, PANC-1, CoLo‑357 and BxPC-3 in our study. In luteolin-treated pancreatic carcinoma cells, typical features of apoptosis were observed. Luteolin increased the expression of the pro-apoptotic protein Bax and decreased the expression of the anti-apoptotic protein Bcl-2, with a concomitant increase in the levels of caspase-3 and cleaved PARP after treatment for 24 h. Luteolin inhibited HUVEC proliferation and vessel growth in CAM in vivo. In addition, the concentration of VEGF in the conditioned medium from human pancreatic carcinoma cells was downregulated by luteolin. Pancreatic carcinoma cells, pretreated with luteolin, could decrease the capillary-like structure formation by HUVEC, which was analyzed by a co-culture system. The abatement of VEGF secretion was related to the inhibition of VEGF mRNA expression, which may be regulated by inhibiting the transcription activity of nuclear transcription factor NF-κB.

Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.

This review highlights the recent advances in research related to the role of IDO in immune escape in cancer and novel small-molecule IDO inhibitors with an emphasis on their chemical structures and modes of action.

Sequential biomimetic elaborations, featured by CrO(3)-mediated oxidative lactonization, and DDQ-involved oxidative enol-lactonization, ensured the concise total synthesis of (+)-chloranthalactone F.