2-Acetylpyridine- and 2-benzoylpyridine-derived thiosemicarbazones and their antimony(III) complexes exhibit high anti-trypanosomal activity

Complexes [Sb(2Ac4oClPh)Cl₂] (1), [Sb(2Ac4oFPh)Cl₂] (2), [Sb(2Ac4oNO₂Ph)Cl₂] (3), [Sb(2Bz4oClPh)Cl₂] (4), [Sb(2Bz4oFPh)Cl₂] (5) and [Sb(2Bz4oNO₂Ph)Cl₂] (6) were obtained with 2-acetylpyridine-N(4)-ortho-chlorophenyl thiosemicarbazone (H2Ac4oClPh) and its N(4)-ortho-fluor (H2Ac4oFPh) and N(4)-ortho-nitro (H2Ac4oNO₂Ph) analogues, and with the corresponding 2-benzoylpyridine-derived thiosemicarbazones (H2Bz4oClPh, H2Bz4oFPh, H2Bz4oNO₂Ph). The studied compounds are excellent inhibitors of Trypanosoma cruzi growth. H2Bz4oClPh and complexes (4) and (1) were the most trypanosomicidal.Upon coordination of H2Ac4oClPh to antimony(III) in 1, the therapeutic index (TI) goes from 10.58 to 14.35. However, the best values of TI were found for H2Bz4oClPh (TI = 1240) and H2Ac4oNO₂Ph (TI = 773). Structure-activity relationship (SAR) studies did not allow the establishment of correlations between the anti-trypanosomal activity and physico-chemical parameters, but correlations were found between the cytotoxicities and physico-chemical properties.     

Synthesis and Anti‐tumor Evaluation of B‐ring Modified Caged Xanthone Analogues of Gambogic Acid

Gambogic acid (GA, 1 ), the most prominent member of Garcinia natural products, has been reported to be a promising anti‐tumor agent. Previous studies have suggested that the planar B ring and the unique 4‐oxa‐tricyclo[4.3.1.0^3,7]dec‐2‐one caged motif were essential for anti‐tumor activity. To further explore the structure‐activity relationship (SAR) of caged Garcinia xanthones, two new series of B‐ring modified caged GA analogues 13a – 13e and 15a – 15e were synthesized utilizing a Claisen/Diel‐Alder cascade reaction. Subsequently, these compounds were evaluated for their in vitro anti‐tumor activities against A549, MCF‐7, SMMC‐7721 and BGC‐823 cancer cell lines by MTT assay. Among them, 13b – 13e exhibited micromolar inhibition against several cancer cell lines, being approximately 2–4 fold less potent in comparison to GA. SAR analysis revealed that the peripheral gem‐dimethyl groups are essential for maintaining anti‐tumor activity and substituent group on C1 position of B‐ring has a significant effect on potency, while modifications at C‐2, C‐3 and C‐4 positions are relatively tolerated. These findings will enhance our understanding of the SAR of Garcinia xanthones and lead to the development of simplified analogues as potential anti‐tumor agents.     

Quantitation of SAR97276 in mouse tissues by rapid resolution liquid chromatography‐mass spectrometry

1,12‐Bis[5‐(2‐hydroxyethyl)‐4‐methyl‐1,3‐thiazol‐3‐ium]dodecane dibromide (SAR97276, T3) is a new antimalarial drug, which is currently being evaluated in clinical trials for severe malaria. Drug accumulation inside the parasite and a dual mechanism of action are a major strength of this compound, as it could help delay the development of resistance. The purpose of this article was to develop a rapid resolution LC‐MS method for quantifying SAR97276 in mouse tissues. The LC system consisted of Zorbax Eclipse XDB C8 (1.8 μm, 50×4.6 mm, 60°C) column. Elution with a gradient mobile phase consisting of ACN–trimethylamine‐formate buffer (pH 3) at a flow rate of 1 mL/min yielded sharp, utmost‐resolved peaks within 2 min. Tissue samples were powdered under liquid nitrogen. After protein precipitation with citric acid, SPE using WCX cartridges was used for sample preparation. There was no influence of the matrix on the detection of either SAR97276 or the IS. Assay precision was <13% and accuracy was 90–107%. The lower LOQs were 3.3 μg/kg in brain and 33 μg/kg in liver and heart. This newly developed method was used to study the tissue distribution of SAR97276 in mouse as part of the ongoing development of SAR97276.     

基于二维连续小波变换的SAR图像海洋现象特征检测

 本文对合成孔径雷达(SAR)图像中存在的多种海洋现象,如内波,海洋锋等进行讨论,提出了一种基于二维连续小波变换及能谱思想的新的海洋现象检测方法.针对各种海洋现象在SAR 中反映出来的海浪波形的不同,采用不同的连续小波变换基提取SAR图像中五种典型的海洋现象.通过大量试验,证实了该方法在多种海洋现象的定位检测中的有效性.     

基于非负矩阵分解的SAR图像目标识别

 特征提取是合成孔径雷达自动目标识别的关键技术,同时也是难点问题之一。本文提出了一种基于非负矩阵分解算法与Fisher线性判别方法的合成孔径雷达图像目标识别的方法,通过基于基向量非负加权组合的形式构建SAR目标图像,能充分利用目标的局部空间结构信息提取目标特征信息实现目标识别。首先将水平集分割预处理后的SAR目标图像样本构成初始矩阵,然后利用非负矩阵分解后得到的权向量作为目标图像的特征向量,再通过依据Fisher线性判别构成的分类器,实现对MSTAR数据中3类目标的识别,并与目前已有的几种典型方案进行对比。试验结果表明该方法是可行且有效的,并能够明显提高对目标识别的稳定性和正确率。     

面阵MIMO-SAR大测绘带成像

 提出一种基于面阵MIMO-SAR(Multiple Input Multiple Output Synthetic Aperture Radar)模型结合脉内扫描技术、二维空域联合处理以及频带合成技术实现高信噪比、二维高分辨大测绘带成像方法。文中首先提出了面阵SAR脉内扫描多发多收模型;分析了面阵MIMO-SAR模型下脉内扫描技术对系统信噪比性能的改善。针对脉内扫描引起的距离模糊以及低PRF(Pulse Repetition Frequency)导致的多普勒模糊,提出了二维空域联合处理方法;同时利用多发多收模型获得多个空间自由度进行频带合成实现高距离分辨。该面阵MIMO-SAR模型实现了高信噪比、二维高分辨大测绘带成像,打破了传统高分辨与大测绘带以及高信噪比与大测绘带的矛盾。仿真实验验证了本文方法的有效性。     

基于微动调制的SAR新型有源干扰方法

 借鉴微动调制思想,提出了一种SAR新型有源干扰方法。详细确定了各关键干扰参数,分析了干扰信号的成像结果,给出了一种基于数字射频存储技术的干扰实施方案,讨论了侦察误差对干扰效果的影响,并进行了基于实测数据的实验分析。结果表明,该干扰样式具有距离向相干处理、方位向部分相干处理的特点,可实现方位向多假欺骗的目的,是一种有效稳健的干扰方法。配合已装备或研制中的各类SAR干扰设备,可增强重要目标的防御能力和生存能力。     

SAR图像斑点噪声抑制方法的研究比较

本文在分析SAR图像斑点噪声特性的基础上,对几种常见的空间域和变换域的斑点噪声抑制方法进行研究,总结了它们的数学基础和性能评价标准,并选择真实的SAR图像进行对比实验,得到一些有用的结论。     

基于视觉系统模型的SAR图像压缩方法

提出一种基于视觉模型的合成孔径雷达(SAR)图像压缩方法,对SAR图像分解后不同频带的小波系数结合其能量分布和人眼对不同频率段的敏感度采用可变步长进行量化与压缩编码,应用嵌入式小波图像压缩算法,以峰值信噪比和均方误差等作为评价指标,对比进行了实验.结果表明,在保证压缩比不变的前提下,采用本算法获得的恢复图像的主观质量有所提高,较好地保留了图像的纹理细节,提高了图像的峰值信噪比.     

基于SPECAN技术的子孔径RD成像算法

由于弹载SAR平台运行速度快、机动性大、运动和姿态存在随机偏差、时实性成像要求高等特点,提出了基于SPECAN技术的子孔径RD成像算法。在距离向,采用匹配滤波技术实现距离向高分辨。在方位向,采用子孔径处理的SPECAN算法。通过仿真结果可以验证,基于SPECAN技术的子孔径RD成像算法有效的减少了数据处理量,降低对弹体存储空间的要求,很好地满足了实时成像要求,提高了导弹的打击精度