Design and Synthesis of Vandetanib Derivatives Containing Nitroimidazole Groups as Tyrosine Kinase Inhibitors in Normoxia and Hypoxia

Sixteen novel epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)-2 inhibitors (nitroimidazole-substituted 4-anilinoquinazoline derivatives (16a–p)) were designed and prepared via the introduction of a nitroimidazole group in the piperidine side chain and modification on the aniline moiety of vandetanib. Preliminary biological tests showed that comparing with vandetanib, some target compounds exhibited excellent EGFR inhibitory activities and anti-proliferative over A549/H446 cells in hypoxia. Meanwhile, several of the above compounds demonstrated better bioactivity than vandetanib in VEGF gene expression inhibition. Owing to the excellent IC50 value (1.64 μmol/L), the inhibition ratios of 16f over A549 and H446 cells were 62.01% and 59.86% at the concentration of 0.5 μM in hypoxia, respectively. All of these results indicated that 16f was a potential cancer therapeutic agent in hypoxia and was worthy of further development

Characteristics and control factors of feldspar dissolution in gravity flow sandstone of Chang 7 Member, Triassic Yanchang Formation, Ordos Basin, NW China

To clarify the formation and distribution of feldspar dissolution pores and predict the distribution of high-quality reservoir in gravity flow sandstone of the 7th member of Triassic Yanchang Formation (Chang 7 Member) in the Ordos Basin, thin sections, scanning electron microscopy, energy spectrum analysis, X-ray diffraction whole rock analysis, and dissolution experiments are employed in this study to investigate the characteristics and control factors of feldspar dissolution pores. The results show that: (1) Three types of diagenetic processes are observed in the feldspar of Chang 7 sandstone in the study area: secondary overgrowth of feldspar, replacement by clay and calcite, and dissolution of detrital feldspar. (2) The feldspar dissolution of Chang 7 tight sandstone is caused by organic acid, and is further affected by the type of feldspar, the degree of early feldspar alteration, and the buffering effect of mica debris on organic acid. (3) Feldspars have varying degrees of dissolution. Potassium feldspar is more susceptible to dissolution than plagioclase. Among potassium feldspar, orthoclase is more soluble than microcline, and unaltered feldspar is more soluble than early kaolinized or sericitized feldspar. (4) The dissolution experiment demonstrated that the presence of mica can hinder the dissolution of feldspar. Mica of the same mass has a significantly stronger capacity to consume organic acids than feldspar. (5) Dissolution pores in feldspar of Chang 7 Member are more abundant in areas with low mica content, and they improve the reservoir physical properties, while in areas with high mica content, the number of feldspar dissolution pores decreases significantly

Efficient Biosynthesis of Phosphatidylserine in a Biphasic System through Parameter Optimization

Phosphatidylserine (PS) has significant biological and nutritional effects and finds wide applications in the food, pharmaceutical, and chemical industries. To produce high-value PS efficiently, phospholipase D (PLD)-induced transphosphatidylation of low-value phosphatidylcholine (PC) with L-serine has been explored. In this research, we purified recombinant PLD from Streptomyces antibioticus SK-3 using ion exchange chromatography and gel filtration chromatography. Subsequently, we thoroughly characterized the purified enzyme and optimized the transphosphatidylation conditions to identify the most favorable settings for synthesizing PS in a biphasic system. The purified recombinant PLD displayed a robust transphosphatidylation function, facilitating efficient catalysis in the synthesis of PS. Under the optimal conditions (butyl acetate/enzyme solution 1:1, L-serine 160 mg/mL, soybean lecithin 2 mg/mL, and MgCl2 15 mM, at 50 °C for 2.5 h with shaking), we achieved a conversion rate of 91.35% and a productivity of 0.73 g/L/h. These results demonstrate the applicability of the process optimization strategy for using the candidate enzyme in the efficient synthesis of PS. Overall, this study presents a novel and scalable approach for the efficient large-scale synthesis of PS