Synthesis and biological evaluation of benzomorpholine derivatives as novel EZH2 inhibitors for anti-non-small cell lung cancer activity

The histone lysine methyltransferase EZH2 has been reported to play important roles in cancer aggressiveness, metastasis and poor prognosis. In this study, a series of benzomorpholine derivatives were synthesized and biologically evaluated as EZH2 inhibitors. The target compounds were obtained in good yields from 3-amino-5-bromo-2-hydroxybenzoic acid via cyclization, Suzuki coupling and amidation as the key steps. A preliminary optimization study led to the discovery of several potent novel EZH2 inhibitors (6b, 6c, 6x and 6y). Moreover, 6y inhibited the A549 and NCI-H1975 cell lines (IC₅₀?=?1.1 µM and 1.1 µM, respectively). Further studies indicated that 6y can reduce EZH2 expression in intact cells and cause cell arrest in the G2/M phase.

     

Phase Behavior and Thermal Properties for Binary Blends of Bacterial Poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate)s with Narrow‐Comonomer‐Unit Compositional Distribution

The miscibility and the effect of compositional distribution on physical properties were investigated for binary blends of biosynthesized poly(3‐hydroxybutyrate) [P(3HB)] and comonomer compositionally fractionated poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate)s [P(3HB‐co‐3HH)] with narrow compositional distribution. Biosynthesized P(3HB‐co‐3HH) samples were compositionally fractionated using solvent (chloroform)/nonsolvent (n‐heptane) mixtures. The binary blends of fractionated P(3HB‐co‐3HH)s with different 3HH unit content were prepared by casting from solution in chloroform. The miscibility and the thermal properties of these blends were analyzed by differential scanning calorimetry (DSC). It was found that the two components are miscible in the amorphous phase when the difference in 3HH unit content between the two component polymers of these blends is less than 20 mol‐%, subsequently they are immiscible when the difference is larger than 30 mol‐%. By comparing the thermal properties of the binary blends of fractions, with those for the fractions themselves, and with those for the bacterially as‐produced unfractionated copolyesters, the effects of compositional distribution on the properties of copolyesters were discussed.

Glass transition temperatures of blends PHB/H10, H10/H20, and PHB/H20 versus total 3HH unit content in the blends. The solid lines are the best fits of the experimental results of the P(3HB‐co‐3HH) fractions with narrow compositional distribution.     

铽-钇-柠檬酸-1,10-菲咯啉的合成与发光

在乙醇溶液中,分别合成了铽与柠檬酸配位的二元配合物,铽、柠檬酸、1,10-菲咯啉配位的三元配合物和铽、钇与柠檬酸、1,10-菲咯啉配位的多核稀土有机三元配合物.通过元素分析、红外光谱等技术确定了配合物的组成与结构,讨论了配合物的成键特性.通过紫外吸收光谱研究了配体传能机制.通过激发与发射光谱测试了配合物的荧光性质.结果表明,当钇掺入配合物后,能极大地增强铽的特征荧光,当铽和钇的摩尔比为73时,能得到相应的铽的荧光最强的配合物.     

三类有效预处理子的关系及其优化

针对一类由时谐抛物方程约束的最优控制问题导出的分块$2\times2$复线性方程组,进一步研究了三类有效的块预处理子,推导了这三类预处理子间的关系,结论表明三个预处理矩阵的特征值由同一个矩阵确定.通过分析预处理矩阵的谱性质,获得了有效的参数选择策略,可以进一步改进和优化现有结果,同时获得了预处理矩阵的精确特征值分布,并证明了此结果是目前文献中最优结果.最后,给出实例,不仅验证了优化的预处理子和迭代方法的有效性,而且说明了理论结果是令人信服的.     

Recollements,idempotent completions and t-structures of triangulated categories

We first prove that the idempotent completion of a right or left recollement of triangulated categories is still a right or left recollement, then show that the t-structure on a triangulated category is compatible with taking idempotent completion. Finally, an application of the main theorem is given, which is focused on the boundedness and nondegeneration of the t-structure induced by a recollement and its idempotent completion.     

2,3-二氯-5,6-二氰基苯醌/H~+作用下4-苯亚甲基-3-异色酮的分子内氧化偶联反应

多甲氧基菲-9-甲酸及酯是合成娃儿藤生物碱及其类似物的关键中间体.以4-(3,4-二甲氧基苯亚甲基)-6,7-二甲氧基-3-异色酮(6)为底物,2,3-二氯-5,6-二氰基苯醌(DDQ)/CH3SO3H作为氧化体系,没有得到预期的多甲氧基菲-9-甲酸内酯(1),意外产物经核磁共振等确定为两个新的3-取代苯基香豆素2,3.进一步的实验研究显示:底物发生分子内脱氢偶联为香豆素2而非菲环化合物1,是因为异色酮6苯环A上2位取代基的存在所致,其内酯环开环化合物10以及2,3-二苯基丙烯酸(12)的对比实验印证了该取代基对脱氢偶联反应选择性的影响;异色酮6氧化偶联为香豆素2的反应机理可能为酸解开环以及途经自由基正离子的脱氢偶联,香豆素3为DDQ氧化2的前体化合物8所得.     

Molecular designing and DFT investigation of novel alternating donor–acceptor dibenzo[b,d]thiophen-based systems: from monomer to polymer

The structures and properties of dibenzo[b,d]thiophene (DBT) based alternating donor–acceptor conjugated oligomers, in which thieno[3,4-b]pyrazine (TP), thieno[3,4-b]thiadiazole (TD), and [1,2,5]thiadiazolo[3,4-e]thieno[3,4-b]pyrazine (TTP) as acceptors, and their periodic polymers were investigated by the density function theory (DFT) at the B3LYP/6-31G(d) level. The bond length, electron density at bond critical points (BCPs) and nucleus-independent chemical shift (NICS) are analyzed and correlated with the conductive properties. NICS shows that the conjugation degree is increased with main chain extension. Research results show the conductive ability of compounds with 1:2 D–A ratio is better than that with 1:1 D–A ratio. The reorganization energies and energy bands also are considered. The results suggest that (BTDDBT) _n and (BTPDDBT) _n have small reorganization energy (0.163 and 0.152 eV, respectively) and quite low energy gap (0.73 and 0.56 eV, respectively), which indicate that they may be potential organic conductive materials.     

结构优化半解析灵敏度及误差修正改进算法

提出结构半解析灵敏度分析及其针对刚体位移的误差修正方法的改进算法, 构建灵敏度分析与误差修正项可分离形式. 该方法实现简便, 数值精度不受摄动步长与单元数目的影响. 首先从总体角度推得静力问题的误差修正半解析灵敏度分析方法, 提出了位移误差修正灵敏度列式, 并给出算法实施途径; 然后将此思路推广于自振频率、屈曲临界载荷问题, 提出了相应的计算步骤. 随后, 给出梁单元与壳单元误差修正项的具体推导方法, 并分别使用两种单元构建有限元模型进行算例测试. 结果表明, 该方法适用于多种分析类型, 数值精度不受单元数目与摄动步长的影响. 由于灵敏度分析与误差修正项可以分开计算, 该方法支持将误差修正项直接叠加于灵敏度求解结果进行误差修正, 使已有灵敏度分析程序得到充分利用. 尤其对于复杂工程结构的优化设计, 特别是形状优化设计以及尺寸、形状混合优化设计, 相比于原误差修正方法, 实现更为简便, 效率有所提升, 能为半解析灵敏度分析方法及其程序实现提供新的思路.