SAR Studies of the Leupyrrins: Design and Total Synthesis of Highly Potent Simplified Leupylogs

Leupyrrins are highly potent antifungal agents. A structure–activity-relationship study of natural and synthetic derivatives is reported which reveals important insights into the biological relevance of several structural subunits leading to the discovery of highly potent but drastically simplified leupylogs that incorporate a stable and readily available aromatic side chain. For their synthesis a concise strategy is described that enables a short and versatile access.     

山西清徐地裂缝形变的InSAR监测分析

山西清徐地裂缝是近年汾渭盆地中活动最为剧烈的地裂缝之一,对耕地、道路和建筑物均造成了严重的破坏。为了监测该地裂缝的活动特征并推测其活动原因,采用差分合成孔径雷达干涉测量技术对该区域的地表形变进行了面状监测。由于受农田覆盖导致的严重时间去相干的影响,本文采用2007年时隔仅为70d的两景Envisat ASAR数据进行了解算,获取了该时间段清徐地区的整体地表形变,特别是清徐地裂缝两侧的形变梯度信息。结果显示: 清徐地裂缝南侧有一个长轴约为2km的地面沉降区域。进一步通过两条平行于地裂缝的剖线和多条垂直于地裂缝的剖线对该地裂缝形变的空间特征进行了分析,结果显示: 清徐地裂缝南侧为主要的形变区域,地裂缝最大的影响宽度达100m,而且地裂缝的不同地段的活动强度也不同, 70d的最大差异形变达5cm。从地裂缝与断裂的空间来看,该地裂缝位置受到交城断裂的控制,而推测近年地裂缝的异常活动则源于地裂缝南侧沉降中心的出现。     

Synthesis and Anti‐tumor Evaluation of Novel C‐37 Modified Derivatives of Gambogic Acid

Gambogic acid (GA, 1 ), the most prominent representative of Garcinia natural products, has been reported to be a promising anti‐tumor agent. In order to further explore the structure‐activity relationship of GA and discover novel GA derivatives as anti‐tumor agents, 17 novel C‐37 modified derivatives of GA were synthesized and evaluated for their in vitro anti‐tumor activities against A549, HCT‐116, BGC‐823, HepG2 and MCF‐7 cancer cell lines. Among them, 11 compounds were found to be more potent than GA against some cancer cell lines. Notably, compound 8 was almost 5–10 folds more active than GA against A549 and BGC‐823 cell lines with the IC₅₀ values of 0.12 µmol·L^?1 and 0.57 µmol·L^?1, respectively. Chemical modification at C‐37 position of GA by introducing of hydrophilic amines could lead to increased activity and improved drug‐like properties. These findings will enhance our understanding of the structure‐activity relationship (SAR) of GA and lead to the discovery of novel GA derivatives as potential anti‐tumor agents.     

Synthesis,Crystal Structures,and Fungicidal Activity of Novel 1,5‐Diaryl‐3‐(glucopyranosyloxy)‐1H‐pyrazoles

Five novel pyrazole‐coupled glucosides, 1,5‐diaryl‐1H‐pyrazol‐3‐yl 2,3,4,6‐tetra‐O‐acetyl‐β‐D ‐glucopyranosides 5a – 5e , were synthesized by the phase‐transfer catalytic reaction of 1,5‐diaryl‐1H‐pyrazol‐3‐ols 4a – 4e with acetobromo‐α‐D ‐glucose in H₂O/CHCl₃ under alkaline conditions, using Bu₄N⁺Br^? as catalyst. Then, glucosides 5a – 5c were deacetylated in a solution of Na₂CO₃/MeOH to yield the 1,5‐diaryl‐3‐(β‐D ‐glucopyranosyloxy)‐1H‐pyrazoles 6a – 6c . Their structures were characterized by ¹H,¹H‐COSY, ¹H‐, ¹³C‐, and ¹⁹F‐NMR spectroscopy, as well as elemental analysis. The structures of 5d and 6c were also determined by single‐crystal X‐ray diffraction analysis. A preliminary in vitro bioassay indicated that compounds 4e and 5d exhibited excellent‐to‐medium fungicidal activity against Sclerotinia sclerotiorum at the dosage of 10 μg/ml.     

RF-related heating assessment of extracranial neurosurgical implants at 7 T

Purpose

The purpose was to evaluate radiofrequency (RF)-related heating of commonly used extracranial neurosurgical implants in 7-T magnetic resonance imaging (MRI).

Materials and methods

Experiments were performed using a 7-T MR system equipped with a transmit/receive RF head coil. Four commonly used titanium neurosurgical implants were studied using a test procedure adapted from the American Society for Testing and Materials Standard F2182-11a. Implants (n = 4) were tested with an MRI turbo spin echo pulse sequence designed to achieve maximum RF exposure [specific absorption rate (SAR) level = 9.9 W/kg], which was further validated by performing calorimetry. Maximum temperature increases near each implant's surface were measured using fiberoptic temperature probes in a gelled-saline-filled phantom that mimicked the conductive properties of soft tissue. Measurement results were compared to literature data for patient safety.

Results

The highest achievable phantom averaged SAR was determined by calorimetry to be 2.0 ± 0.1 W/kg due to the highly conservative SAR estimation model used by this 7-T MR system. The maximum temperature increase at this SAR level was below 1.0 °C for all extracranial neurosurgical implants that underwent testing.

Conclusion

The findings indicated that RF-related heating under the conditions used in this investigation is not a significant safety concern for patients with the particular extracranial neurosurgical implants evaluated in this study.     

Research on synthetic aperture radar imaging technology of one-dimensional layered rough surfaces

A quick and exact imaging method for one-dimensional layered rough surfaces is proposed in this paper to study the scattering characteristics of a layered medium that exists widely in nature.The boundary integral equations of layered rough surfaces are solved by using the propagation-inside-layer expansion combined with the forward and backward spectral acceleration method(PILE+FB-SA),and the back scattering data are obtained.Then,a conventional synthetic aperture radar(SAR) imaging procedure called back projection method is used to generate a two-dimensional(2D) image of the layered rough surfaces.Combined with the relative dielectric permittivity of realistic soil,the random rough surfaces with Gauss spectrum are used to simulate the layered medium with rough interfaces.Since the back scattering data are computed by using the fast numerical method,this method can be used to study layered rough surfaces with any parameter,which has a great application value in the detection and remote sensing areas.     

Optimizing Dvl PDZ domain inhibitor by exploring chemical space

Because of advances in the high-throughput screening technology, identification of a hit that can bind to a target protein has become a relatively easy task; however, in the process of drug discovery, the following hit-to-lead and lead optimization still remain challenging. In a typical hit-to-lead and lead optimization process, the analogues of the most promising hits are synthesized for the development of structure–activity relationship (SAR) analysis, and in turn, in the effort of optimization of lead compounds, such analysis provides guidance for the further synthesis. The synthesis processes are usually long and labor-intensive. In silico searching has becoming an alternative approach to explore SAR especially with millions of compounds ready to be screened and most of them can be easily obtained. Here, we report our discovery of 15 new Dishevelled PDZ domain inhibitors by using such an approach. In our studies, we first developed a pharmacophore model based on NSC668036, an inhibitor previously identified in our laboratory; based on the model, we then screened the ChemDiv database by using an algorithm that combines similarity search and docking procedures; finally, we selected potent inhibitors based on docking analysis and examined them by using NMR spectroscopy. NMR experiments showed that all the 15 compounds we chose bound to the PDZ domain tighter than NSC668036.     

合成孔径雷达图像的Contourlet域空间选择滤波降斑算法

合成孔径雷达(SAR)图像的相干斑噪声降低了影像分割和分类的效果,会导致影像判识困难。结合Con-tourlet系数的结构特点和SAR图像相干斑乘性噪声模型,提出了一种新的基于Contourlet变换的降斑算法。该算法利用信号与噪声在Contourlet域尺度间相关性的不同,通过空间选择滤波对系数进行分类,采用混合分布模型,实现了SAR图像的降斑处理。实验结果表明,该算法不仅能有效地抑制相干斑,而且还能有效地保护图像的细节特征。     

Repetition time and flip angle variation in SPRITE imaging for acquisition time and SAR reduction

Single point imaging methods such as SPRITE are often the technique of choice for imaging fast-relaxing nuclei in solids. Single point imaging sequences based on SPRITE in their conventional form are ill-suited for in vivo applications since the acquisition time is long and the SAR is high. A new sequence design is presented employing variable repetition times and variable flip angles in order to improve the characteristics of SPRITE for in vivo applications. The achievable acquisition time savings as well as SAR reductions and/or SNR increases afforded by this approach were investigated using a resolution phantom as well as PSF simulations. Imaging results in phantoms indicate that acquisition times may be reduced by up to 70% and the SAR may be reduced by 40% without an appreciable loss of image quality.     

Quinoxaline Moiety: A Potential Scaffold against Mycobacterium tuberculosis

Background. The past decades have seen numerous efforts to develop new antitubercular agents. Currently, the available regimens are lengthy, only partially effective, and associated with high rates of adverse events. The challenge is therefore to develop new agents with faster and more efficient action. The versatile quinoxaline ring possesses a broad spectrum of pharmacological activities, ensuring considerable attention to it in the field of medicinal chemistry. Objectives. In continuation of our program on the pharmacological activity of quinoxaline derivatives, this review focuses on potential antimycobacterial activity of recent quinoxaline derivatives and discusses their structure—activity relationship for designing new analogs with improved activity. Methods. The review compiles recent studies published between January 2011 and April 2021. Results. The final total of 23 studies were examined. Conclusions. Data from studies of quinoxaline and quinoxaline 1,4-di-N-oxide derivatives highlight that specific derivatives show encouraging perspectives in the treatment of Mycobacterium tuberculosis and the recent growing interest for these scaffolds. These interesting results warrant further investigation, which may allow identification of novel antitubercular candidates based on this scaffold.