Design,Synthesis, and Antifungal Activities of New β‐Methoxyacrylate Analogues

Strobilurins have become one of the most important classes of agricultural fungicides. To search for new strobilurin derivatives with high activity against resistant pathogens, a series of new β‐methoxyacrylate analogues containing substituted pyrimidine in the side chain with strobilurin pharmacophore were synthesized and their biological activities were tested. The compounds were confirmed and characterized by ¹H‐NMR, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds 1 exhibited potent antifungal activities against Colletotrichum orbiculare, Botrytis cinerea Pers and Phytophthora capsici Leonian at a concentration of 50 μg mL^?1. Notably, compound 1b (R = 2,5‐dimethylphenyl) showed better antifungal activity against all the tested fungi than the commercial strobilurin fungicide azoxystrobin.     

Discovery of Novel Sultone Fused Berberine Derivatives as Promising Tdp1 Inhibitors

A new type of berberine derivatives was obtained by the reaction of berberrubine with aliphatic sulfonyl chlorides. The new polycyclic compounds have a sultone ring condensed to C and D rings of a protoberberine core. The reaction conditions were developed to facilitate the formation of sultones with high yields without by-product formation. Thus, it was shown that the order of addition of reagents affects the composition of the reaction products: when sulfochlorides are added to berberrubine, their corresponding 9-O-sulfonates are predominantly formed; when berberrubine is added to pre-generated sulfenes, sultones are the only products. The reaction was shown to proceed stereo-selectively and the cycle configuration was confirmed by 2D NMR spectroscopy. The inhibitory activity of the synthesized sultones and their 12-brominated analogs against the DNA-repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1), an important target for a potential antitumor therapy, was studied. All derivatives were active in the micromolar and submicromolar range, in contrast to the acyclic analogs and 9-O-sulfonates, which were inactive. The significance of the sultone cycle and bromine substituent in binding with the enzyme was confirmed using molecular modeling. The active inhibitors are mostly non-toxic to the HeLa cancer cell line, and several ligands show synergy with topotecan, a topoisomerase 1 poison in clinical use. Thus, novel berberine derivatives can be considered as candidates for adjuvant therapy against cancer.     

Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC₅₀ values in the 0.35–0.57 µM range. The cytotoxicity was determined in the HeLa, HCT-116 and SW837 cancer cell lines; moderate CC₅₀ (µM) values were seen from the mid-teens to no effect at 100 µM. Furthermore, citral derivative 20c, α-pinene-derived compounds 20f, 20g and 25c, and the citronellic acid derivative 25b were found to have a sensitizing effect in conjunction with topotecan in the HeLa cervical cancer and colon adenocarcinoma HCT-116 cell lines. The ligands are predicted to bind in the catalytic pocket of Tdp1 and have favorable physicochemical properties for further development as a potential adjunct therapy with Top1 poisons.     

Heterocyclic compounds as antiviral drugs: Synthesis,structure–activity relationship and traditional applications

A virus outbreak challenges the economic, medical, and public health infrastructure worldwide. More than one virus capable of triggering diseases have been identified per year since 1972, which requires the development of new ways of treatment and prevention, however, such processes are not rapid and easy. With the pandemic scenario experienced since early 2020, several drugs with well-known purposes have gained prominence, due to speculation of their use in the treatment against the new coronavirus. Among the main drugs studied, the vast majority contain a heterocyclic structure. In this review, we presented the traditional and efficient synthesis of 15 drugs that have been studied for the COVID-19 treatment, containing in their structure heterocycles like indole, quinoline, pyrimidone, tetrahydrofuran, pyrrolidine, triazole, pyridazine, pyrazole, pyrrolopyrimidine, azetidine, pyrrolotriazine, pyrazine, tetrahydropyran, benzofuran, spiroketal, and thiazole. Furthermore, we have shown the original applications, as well as their structure–activity relationship and what is their situation as a drug candidate against COVID-19. Thus, the objective was to consolidate the main synthetic and pharmacological aspects involving clinically developed heterocycles that at some point were presented as promising against SARS-CoV-2.     

A regularised boundary element formulation for contactless SAR evaluations within homogeneous and inhomogeneous head phantoms

This work presents a Boundary Element Method (BEM) formulation for contactless electromagnetic field assessments. The new scheme is based on a regularised BEM approach that requires the use of electric measurements only. The regularisation is obtained by leveraging on an extension of Calderón techniques to rectangular systems leading to well-conditioned problems independent of the discretisation density. This enables the use of highly discretized Huygens surfaces that can be consequently placed very near to the radiating source. In addition, the new regularised scheme is hybridised with both surfacic homogeneous and volumetric inhomogeneous forward BEM solvers accelerated with fast matrix–vector multiplication schemes. This allows for rapid and effective dosimetric assessments and permits the use of inhomogeneous and realistic head phantoms. Numerical results corroborate the theory and confirms the practical effectiveness of all newly proposed formulations.     

Comparison of criteria used to access carcinogenicity in CPANN QSAR models versus the knowledge-based expert system Toxtree

The primary goal of this study was to describe and compare the criteria used to assess carcinogenic activity. The statistically-based predictive quantitative structure–activity relationship (QSAR) models based on the counter propagation artificial neural network (CPANN) algorithm, and knowledge-based expert systems based on a decision tree structural alert (SA) approach (Toxtree application), were considered. The integration of the QSAR (CPANN models) and SAR (Toxtree SA application) approach contributed to the mechanistic understanding of the QSAR model considered. The mapping technique inherent to CPANN Kohonen enables us to relate the similarities or dissimilarities within a congeneric set of chemicals with particular SAs for carcinogenicity. The focus of our investigations was the similarities and dissimilarities of the features used in the QSAR and SAR methods. Due to the complexity of the carcinogenic endpoint, the integration of different approaches allows the models to be improved and provides a valuable technique for evaluating the safety of chemicals.     

Segmentation of synthetic aperture radar image using multiscale information measure-based spectral clustering

A multiscale information measure （MIM）, calculable from per-pixel wavelet coefficients, but relying on global statistics of synthetic aperture radar （SAR） image, is proposed. It fully exploits the variations in speckle pattern when the image resolution varies from course to fine, thus it can capture the intrinsic texture of the scene backscatter and the texture due to speckle simultaneously. Graph spectral segmen- tation methods based on MIM and the usual similarity measure are carried out on two real SAR images. Experimental results show that MIM can characterize texture information of SAR image more effectively than the commonly used similarity measure.     

Multi-sensors SAR system for real-time dosimetry assessment

A multi-sensor test-bench for determining the SAR (specific absorption rate) due to wireless devices emitting in equivalent human tissues is presented. Real-time SAR assessment is proposed considering a spatially distributed multiprobe test-bench. In comparison with a multi-axial robot SAR system, the proposed one does not require any displacement, thus reducing drastically acquisition time, once parallel data acquisition and interpolation techniques are employed for accelerating measurements.     

合成孔径雷达光学处理器的检测方法

本文以一个通用合成孔径雷达光学处理器(简称OSARP)的检测为例,来说明OSARP的检测方法。给出OSARP的每个可调部件与合成孔径雷达(简称SAR)数据片的各特征参数间的关系,通过测量调整量求得OSARP的适用范围;用普通检测目标加位移透镜,来检测OSARP的成像质量。同时用模拟的SAR数据片,以另一种方法对OSARP做检测,结果相同。最后处理了真实SAR数据片,用来展示SAR和OSARP的综合成像质量。文中给出一些实验照片和数据,结果表明,本检测方法是可行的。