Aryl-oxadiazole Schiff bases: Synthesis, α-glucosidase in vitro inhibitory activity and their in silico studies

α-Glucosidase enzyme is a therapeutic target for diabetes mellitus and its inhibitors play a vital role in the treatment of this disease. A new series of aryl-oxadiazole Schiff bases (1–18) were synthesized and evaluated for α-glucosidase inhibitory potential. Fifteen compounds 1–8, 11–13, and 15–18 showed excellent inhibition with IC₅₀ values ranging from 0.30 ± 0.2 to 35.1 ± 0.80 µM as compared to the standard inhibitor acarbose (IC₅₀ = 38.45 ± 0.80 µM), nonetheless, the remaining compounds were found to have moderate activity. Among the series, compounds 7 (IC₅₀ = 0.30 ± 0.2 μM) with hydroxy groups at phenyl rings on either side of the oxadiazole ring was identified as the most potent inhibitor of α-glucosidase. The molecular docking studies were conducted to understand the binding mode of active inhibitors with the active site of enzyme and results supported the experimental data.     

Plasmodial Kinase Inhibitors Targeting Malaria: Recent Developments

Recent progress in reducing malaria cases and ensuing deaths is threatened by factors like mutations that induce resistance to artemisinin derivatives. Multiple drugs are currently in clinical trials for malaria treatment, including some with novel mechanisms of action. One of these, MMV390048, is a plasmodial kinase inhibitor. This review lists the recently developed molecules which target plasmodial kinases. A systematic review of the literature was performed using CAPLUS and MEDLINE databases from 2005 to 2020. It covers a total of 60 articles and describes about one hundred compounds targeting 22 plasmodial kinases. This work highlights the strong potential of compounds targeting plasmodial kinases for future drug therapies. However, the majority of the Plasmodium kinome remains to be explored.     

An evaluation of selected (Q)SARs/expert systems for predicting skin sensitisation potential

Predictive testing to characterise substances for their skin sensitisation potential has historically been based on animal models such as the Local Lymph Node Assay (LLNA) and the Guinea Pig Maximisation Test (GPMT). In recent years, EU regulations, have provided a strong incentive to develop non-animal alternatives, such as expert systems software. Here we selected three different types of expert systems: VEGA (statistical), Derek Nexus (knowledge-based) and TIMES-SS (hybrid), and evaluated their performance using two large sets of animal data: one set of 1249 substances from eChemportal and a second set of 515 substances from NICEATM. A model was considered successful at predicting skin sensitisation potential if it had at least the same balanced accuracy as the LLNA and the GPMT had in predicting the other outcomes, which ranged from 79% to 86%. We found that the highest balanced accuracy of any of the expert systems evaluated was 65% when making global predictions. For substances within the domain of TIMES-SS, however, balanced accuracies for the two datasets were found to be 79% and 82%. In those cases where a chemical was within the TIMES-SS domain, the TIMES-SS skin sensitisation hazard prediction had the same confidence as the result from LLNA or GPMT.     

Conformationally restricted goniofufurone mimics with halogen,azido or benzoyloxy groups at the C-7 position: Design,synthesis and antiproliferative activity

A series of new conformationally restricted goniofufurone mimics, bearing an additional 1,3-dioxan ring and a halogen, azido or benzoyloxy functionality at the C-7 position has been designed and synthesized. The Appel reaction was used for replacement of 7-OH group with Cl or Br functions in tricyclic lactone (3). 7-Iodo derivative (3d) was prepared by using the Ph₃P/I₂/2,6-lutidine reagent system. 7-Fluoro group was introduced by treatment of 3 with DAST, while the corresponding 7-azido and 7-benzoyloxy derivatives have been prepared by multistep sequences. Synthesized products were evaluated for their ability to inhibit growth of selected human malignant cell lines. Structure-activity relationships demonstrated that the nature of a substituent at the C-7 position could enhance the antiproliferative activity of the analogues. The preliminary study on the mechanisms indicated that all synthesized compounds induced apoptosis in 61–77% of K562?cells.     

机载C波段全极化SAR海面风矢量反演理论研究及实验验证

机载全极化SAR海面风矢量反演研究对于近海岸复杂气象条件下风矢量探测具有重要意义. 本文从极化散射理论出发,通过分析全极化SAR探测数据与海面风矢量的关系, 设计了全极化SAR海面风矢量反演方案.依据机载SAR高机动性和全极化两个探测特点, 针对VV极化探测数据,提出了基于最大似然估计的海面风矢量反演方法,并设计了飞行实验方案; 针对VH极化探测数据,提出了通过带约束最优拟合的VH极化海面散射模型反演风速, 再利用CMOD5地球物理模型函数计算风向的海面风矢量反演方法. 利用机载全极化SAR探测的台风'海葵'边缘数据,开展了海面风矢量反演实验研究. 研究结果表明,两种风矢量反演方法均可不借助辅助信息,反演复杂气象条件下的海面风矢量. 前者反演风向、风速的均方根误差分别为18.0°, 1.8 m/s, 后者反演风向、风速的均方根误差分别为9.3°, 1.2 m/s,后者的反演精度优于前者. 这是因为VH极化归一化雷达截面与风向和雷达入射角无关,仅与风速密切相关, 更适合复杂气象条件下的海面风矢量反演. 关键词： 机载全极化SAR 海面风矢量 理论研究 实验验证     

Role of Magnetite Nanoparticles Size and Concentration on Hyperthermia under Various Field Frequencies and Strengths

Magnetite (Fe₃O₄) nanoparticles were synthesized using the chemical coprecipitation method. Several nanoparticle samples were synthesized by varying the concentration of iron salt precursors in the solution for the synthesis. Two batches of nanoparticles with average sizes of 10.2 nm and 12.2 nm with nearly similar particle-size distributions were investigated. The average particle sizes were determined from the XRD patterns and TEM images. For each batch, several samples with different particle concentrations were prepared. Morphological analysis of the samples was performed using TEM. The phase and structure of the particles of each batch were studied using XRD, selected area electron diffraction (SAED), Raman and XPS spectroscopy. Magnetic hysteresis loops were obtained using a Lakeshore vibrating sample magnetometer (VSM) at room temperature. In the two batches, the particles were found to be of the same pure crystalline phase of magnetite. The effects of particle size, size distribution, and concentration on the magnetic properties and magneto thermic efficiency were investigated. Heating profiles, under an alternating magnetic field, were obtained for the two batches of nanoparticles with frequencies 765.85, 634.45, 491.10, 390.25, 349.20, 306.65, and 166.00 kHz and field amplitudes of 100, 200, 250, 300 and 350 G. The specific absorption rate (SAR) values for the particles of size 12.2 nm are higher than those for the particles of size 10.2 nm at all concentrations and field parameters. SAR decreases with the increase of particle concentration. SAR obtained for all the particle concentrations of the two batches increases almost linearly with the field frequency (at fixed field strength) and nonlinearly with the field amplitude (at fixed field frequency). SAR value obtained for magnetite nanoparticles with the highest magnetization is 145.84 W/g at 765.85 kHz and 350 G, whereas the SAR value of the particles with the least magnetization is 81.67 W/g at the same field and frequency.     

Novel Synthetic Routes to Prepare Biologically Active Quinoxalines and Their Derivatives: A Synthetic Review for the Last Two Decades

Quinoxalines, a class of N-heterocyclic compounds, are important biological agents, and a significant amount of research activity has been directed towards this class. They have several prominent pharmacological effects like antifungal, antibacterial, antiviral, and antimicrobial. Quinoxaline derivatives have diverse therapeutic uses and have become the crucial component in drugs used to treat cancerous cells, AIDS, plant viruses, schizophrenia, certifying them a great future in medicinal chemistry. Due to the current pandemic situation caused by SARS-COVID 19, it has become essential to synthesize drugs to combat deadly pathogens (bacteria, fungi, viruses) for now and near future. Since quinoxalines is an essential moiety to treat infectious diseases, numerous synthetic routes have been developed by researchers, with a prime focus on green chemistry and cost-effective methods. This review paper highlights the various synthetic routes to prepare quinoxaline and its derivatives, covering the literature for the last two decades. A total of 31 schemes have been explained using the green chemistry approach, cost-effective methods, and quinoxaline derivatives’ therapeutic uses.     

New Helvolic Acid Derivatives with Antibacterial Activities from Sarocladium oryzae DX-THL3, an Endophytic Fungus from Dongxiang Wild Rice (Oryza rufipogon Griff.)

Three new helvolic acid derivatives (named sarocladilactone A (1), sarocladilactone B (2) and sarocladic acid A (3a)), together with five known compounds (6,16-diacetoxy-25-hy- droxy-3,7-dioxy-29-nordammara-1,17(20)-dien-21-oic acid (3b), helvolic acid (4), helvolinic acid (5), 6-desacetoxy-helvolic acid (6) and 1,2-dihydrohelvolic acid (7)), were isolated from the endophytic fungus DX-THL3, obtained from the leaf of Dongxiang wild rice (Oryza rufipogon Griff.). The structures of the new compounds were elucidated via HR-MS, extensive 1D and 2D NMR analysis and comparison with reported data. Compounds 1, 2, 4, 5, 6 and 7 exhibited potent antibacterial activities. In particular, sarocladilactone B (2), helvolinic acid (5) and 6-desacetoxy-helvolic acid (6) exhibited strongly Staphylococcus aureus inhibitory activity with minimum inhibitory concentration (MIC) values of 4, 1 and 4 μg/mL, respectively. The structure–activity relationship (SAR) of these compounds was primarily summarized.     

一种三相三线与三相四线自适应电能表的设计

针对合成孔径雷达（SAR）清晰成像的特点,为保证雷达天线波束指向稳定,设计了某型机载雷达天线稳定平台。为了消除雷达天线稳定平台控制中存在的非线性及不确定性因素的影响,提出了一种应用于雷达天线稳定平台控制系统的模糊PID控制策略。稳定平台是依据陀螺仪所采集载机的角速度,运用反向运动补偿的原理进行工作。控制策略中,在传统PID控制的基础上引入模糊控制算法,根据跟踪误差信号动态改变PID控制器参数,改善稳定平台的控制效果,完成稳定平台控制器的优化设计。仿真结果表明,优化后的模糊PID控制算法与传统PID控制算法比较,在稳定平台转速控制方面受到的外部干扰影响更小,响应速度更快。因此,基于模糊PID控制算法的雷达天线稳定平台具有更高的稳定性能。