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A series of (2-benzoylethen-1-ol)-containing benzothiazine derivatives was synthesized, and their herbicidal activities were first evaluated. The bioassay results indicated that some of 3-benzoyl-4-hydroxy-2-methyl-2 H -1,2-benzothiazine-1,1-dioxide derivatives displayed good herbicidal activity in greenhouse testing, especially, compound 4w had good pre-emergent herbicidal activities against Brassica campestris , Amaranthus retroflexus and Echinochloa crusgalli even at a dosage of 187.5 g ha −1 . More importantly, compound 4w displayed significant inhibitory activity against Arabidopsis thaliana HPPD and was identified as the most potent candidate with IC 50 value of 0.48 μM, which is better than the commercial herbicide sulctrione (IC 50 = 0.53 μM) and comparable with the commercial herbicide mesotrione (IC 50 = 0.25 μM). The structure–activity relationships was studied and provided some useful information for improving herbicidal activity. The present work indicated that (2-benzoylethen-1-ol)-containing 1,2-benzothiazine motif could be a potential lead structure for further development of novel HPPD inhibiting-based herbicides. [ABSTRACT FROM AUTHOR]

This work described the fabrication of a gold nanoparticles/single-walled carbon nanotubes/glassy carbon electrode containing mono-6-thio-β-cyclodextrin (SH-β-CD) self-assembled monolayer (SH-β-CD/AuNPs/SWCNTs/GCE) and its application for electrochemical determination of methyl parathion (MP) pesticide in solution using square wave anodic stripping voltammetry (SWV) method. The SH-β-CD/AuNPs/SWCNTs nanohybrids had a three-dimensional porous nanostructure with large active surface area, and the SH-β-CD monolayer on AuNPs/SWCNTs surface could greatly enhance the sensitivity and selectivity in detecting MP pesticides. The SWV response of the MP on the SH-β-CD/AuNPs/SWCNTs/GCE was ca. 3.9 and 5.1 times that of MP on the SH-β-CD/AuNPs/GCE and AuNPs/SWCNTs/GCE, respectively. The sensor demonstrated a wide linear response range from 2.0–80.0 nM, with a lower detection limit of 0.1 nM (S/N = 3) using 180 s of preconcentration time. The interference experiments showed that other aromatic insecticide, such as, chlorpyrifos, 2,4-dDichlorophenoxy acetic acid, methamidophos, triazophos, parathion had little influence on the MP signal. The proposed sensor was further employed for detection of MP in the real environmental water sample. [ABSTRACT FROM AUTHOR]

Histone deacetylase 6 (HDAC6) has emerged as a critical regulator of many cellular pathways in tumors due to its unique structure basis and abundant substrate types. Over the past few decades, the role played by HDAC6 inhibitors as anticancer agents has sparked great interest of biochemists worldwide. However, they were less reported for gastric cancer therapy. In this paper, with the help of bioisosteric replacement, in-house library screening, and lead optimization strategies, we designed, synthesized and verified a series of 1,3-diaryl-1,2,4-triazole-capped HDAC6 inhibitors with promising anti-gastric cancer activities. Amongst, compound 9r displayed the best inhibitory activity towards HDAC6 (IC 50 = 30.6 nM), with 128-fold selectivity over HDAC1. Further BLI and CETSA assay proved the high affinity of 9r to HDAC6. In addition, 9r could dose-dependently upregulate the levels of acetylated α-tubulin, without significant effect on acetylated histone H3 in MGC803 cells. Besides, 9r exhibited potent antiproliferative effect on MGC803 cells, and promoted apoptosis and suppressed the metastasis without obvious toxicity, suggesting 9r would serve as a potential lead compound for the development of novel therapeutic agents of gastric cancer. [Display omitted] ● A novel series of 1,3-diaryl-1,2,4-triazole-capped HDAC6 inhibitors were designed and synthesized by the strategies of bioisosteric replacement, in-house library screening, and lead optimization. ● Compound 9r exhibited the best potency to HDAC6 (IC 50 = 30.6 nM), with 128-fold selectivity over HDAC1. ● Compound 9r displayed promising anti-gastric cancer activity without obvious toxicity. [ABSTRACT FROM AUTHOR]

In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound 5d displayed significant advantages in inhibition effect with an IC 50 value of 0.031 μM, and better selectivity between cancer and normal cells than 3-AP and DpC (about 15- and 5-fold improved respectively). Besides, compound 5d showed selective antiproliferative activity in not only other cancer cells but also different gastric cancer cell lines. In-depth mechanism studies showed that compound 5d could induce mitochondria-related apoptosis which might be related to the elevation of intracellular ROS level, and cause cell cycle arrest at S phase. Moreover, 5d could evidently suppress the cell migration and invasion by blocking the EMT (epithelial–mesenchymal transition) process. Consequently, our studies provided a lead optimization strategy of thiosemicarbazone derivatives which would contribute to discover high-efficiency and low-toxicity agents for the treatment of gastric cancer. Image 1 • The design and synthesis were based on lead optimization strategy. • 5d showed higher antiproliferative activity and lower toxicity than 3-AP and DpC. • 5d could induce cell apoptosis, and inhibit the migration and invasion of MGC803 cells. [ABSTRACT FROM AUTHOR]

Abstract: Camellia chekiangoleosa is an important species of genus Camellia. It provides high-quality edible oil and has great ornamental value. The flowers are big and red which bloom between February and March. Flower pigmentation is closely related to the accumulation of anthocyanin. Although anthocyanin biosynthesis has been studied extensively in herbaceous plants, little molecular information on the anthocyanin biosynthesis pathway of C. chekiangoleosa is yet known. In the present study, a cDNA library was constructed to obtain detailed and general data from the flowers of C. chekiangoleosa. To explore the transcriptome of C. chekiangoleosa and investigate genes involved in anthocyanin biosynthesis, a 454 GS FLX Titanium platform was used to generate an EST dataset. About 46,279 sequences were obtained, and 24,593 (53.1%) were annotated. Using Blast search against the AGRIS, 1740 unigenes were found homologous to 599 Arabidopsis transcription factor genes. Based on the transcriptome dataset, nine anthocyanin biosynthesis pathway genes (PAL, CHS1, CHS2, CHS3, CHI, F3H, DFR, ANS, and UFGT) were identified and cloned. The spatio-temporal expression patterns of these genes were also analyzed using quantitative real-time polymerase chain reaction. The study results not only enrich the gene resource but also provide valuable information for further studies concerning anthocyanin biosynthesis. [Copyright &y& Elsevier]