Discovery of pyrrolo[2,3-d]pyrimidine-based molecules as a Wee1 inhibitor template.

In the past decade, Wee1 inhibition has received widespread attention as a cancer therapy. Our research aims to discover effective, selective and drug-like Wee1 inhibitors. Herein, a series of compounds with pyrrolo[2,3-d]pyrimidine-based heterocycles were designed, synthesized and confirmed to inhibit Wee1 kinase. The inhibitors afforded good potency in Wee1 Kinase inhibitory activity in enzymatic assays. These compounds showed strong proliferation inhibition against NCI-1299 cell lines and had acceptable pharmacokinetic properties. These derivatives are promising inhibitors that warrant further evaluation, towards the development of potential anticancer drug.

Effect of piceatannol against malignant melanoma in vivo and in vitro.

OBJECTIVES: To study the antitumor effect of piceatannol (PIC) on malignant melanoma in vitro and in vivo. METHODS: B16F10 cells were cultured in vitro and treated with gradient concentrations of PIC. Cell viability was detected with methyl thiazolyl tetrazolium (MTT) assay; matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), spleen tyrosine kinase (Syk), and p-Syk were detected with Western blot; migration ability was detected with wound healing assay; invasion ability was detected with Transwell assay. Syk expression was suppressed through RNA interference for the detection of the possible mechanism of PIC in melanoma. An in vivo study was established by creating B16F10-bearing mice with intraperitoneal injection of PIC. RESULTS: The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. In vivo study revealed that different concentrations of PIC cangreatly inhibit melanoma progression. CONCLUSIONS: PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.

1-Phenyl-N-(benzothiazol-2-yl)methanimine derivatives as Middle East respiratory syndrome coronavirus inhibitors.

Middle East respiratory syndrome coronavirus (MERS-CoV) poses a serious threat to human health, and currently there are no effective or specific therapies available to treat it. Herein a series of 1-phenyl-N-(benzothiazol-2-yl)methanimine derivatives with inhibitory activity against MERS-CoV are described. The compound 4f with a 50% inhibition concentration value of 0.09 µM is a promising inhibitor that warrants further evaluation, towards the development of potential anti-MERS-CoV drugs.

[Spatial and Temporal Dynamics of Floating Algal Blooms in Lake Chaohu in 2016 and Their Environmental Drivers].

Lake Chaohu has drawn increasing attention due to the occurrence of massive algal blooms. This study applied daily monitoring results from moderate-resolution imaging spectrum-radiometer (MODIS) satellite to extract algal blooms with a floating algal index algorithm and characterize surface floating algal bloom dynamics in 2016 with an algae pixel-growing algorithm. Combining water quality and meteorological data, environmental driving forces of algal blooms in 2016 were explored. The results showed that cyanobacterial blooms occurred throughout the lake from May to November, which is the same as in previous years. Compared with previous years, the initial bloom date was postponed to May, the duration was reduced to 204 days, and the average floating algal bloom area was reduced to 85.53 km2. By investigating the environmental driving forces affecting the algal bloom, it was found that a larger wind speed (△W=0.1 m·s-1), more precipitation (△P=0.8 mm), and a lower sunshine duration (△S=-1.3 h) in spring were the main reasons. When the temperature was suitable, precipitation was the main driving force affecting the monthly variation in algal blooms. The daily average wind speed was also negatively correlated with the algal bloom area (P<0.05). High wind speed can affect the area of algal blooms as well. These results will aid understanding of the situation of cyanobacterial blooms in Lake Chaohu and provide a theoretical basis for dealing with algal blooming and climate change.