手性冠醚的研究进展及一类新型手性冠醚的合成展望

冠醚是一类具有内部空腔的多元醚类化合物,具有手性中心的冠醚即为手性冠醚。异斯特维醇及其衍生物是由天然产物甜菊糖苷酸水解而来的二萜类化合物,具有很好的手性催化和分子识别性能。联萘酚是具有光学活性的联萘型化合物,其具有独特的立体结构,在手性催化和分子识别等方面也都有很好的应用。本文对冠醚,异斯特维醇以及联萘酚的研究现状进行了总结,并对以异斯特维醇及其衍生物和联萘酚为骨架的手性冠醚的合成做出了展望。     

异甜菊醇及其衍生物的合成与应用研究进展

甜菊糖苷是一种天然甜味刑,在酸性条件下水解为异甜菊醇。异甜菊醇具有降血压、降血糖、抗炎和抗肿瘤等生理活性。本文对异甜菊醇及其衍生物在抗炎、抗肿瘤、手性催化和分子识别方面的应用研究进行了总结。     

卡拉胶的生物活性及分子修饰研究进展

卡拉胶作为一种结构独特的硫酸多糖,具有多种生物活性,但因分子量过大,使其在生物医药领域的应用受到限制。文章简要介绍了近年来有关卡拉胶抗病毒、抗肿瘤、抗凝血等生物活性的研究,进一步介绍了卡拉胶分子修饰及其衍生物生物活性的研究进展。     

环糊精应用新进展：构筑分子选择性光学传感器

以环糊精及其衍生物为主体分子,可设计合成分子选择性光化学传感器。本文概述了环糊精及其衍生物在显色型分子识别检测器、荧光传感器及光纤传感器中的应用。     

异喹啉及其衍生物合成方法研究进展

异喹啉及衍生物具有良好的抑菌、抗肿瘤、止痛、抗疟疾、抗心律失齐以及抗艾滋等生物活性,在医药、化工、染料等领域都有广泛的应用。本文主要综述了异喹啉以及衍生物的合成方法及最新进展。     

新型手性硫脲的合成与表征

以天然产物甜菊糖的水解产物异斯特维醇为原料,合成了一种新型手性硫脲,产物结构经NMR、HRMS、IR等验证。并考察了它在直接不对称Aldol反应中与脯氨酸的共催化性能,结果表明具有一定的催化效果。     

手性伯胺-硫脲的合成与应用

以天然产物甜菊糖的水解产物异斯特维醇为起始原料,经过简单反应,设计合成了新型手性伯胺-硫脲,其结构经IR、NMR、HRMS等表征。同时考察了该催化剂在不对称Michael加成反应中的催化性能,结果表明具有一定的催化效果。     

新型异噻唑啉酮衍生物抑菌活性及作用机制研究

研究了新型异噻唑啉酮衍生物的抑菌活性及作用机制。采用滤纸片扩散法测定了20个新型异噻唑啉酮衍生物对5种细菌的抑菌活性;选取5个高抑菌活性衍生物,使用AutoDock软件进行分子对接,分析了其与葡糖胺-6-磷酸合成酶(G-6-P合酶)的相互作用模式;运用密度泛函(DFT)方法对5个高抑菌活性衍生物的分子静电势进行了理论计算。结果表明,以链霉素为阳性对照,有11个衍生物对蜡状芽孢杆菌具有一定的抑制作用,有3个衍生物对枯草芽孢杆菌具有一定的抑制作用,有3个衍生物对烟草青枯病菌具有一定的抑制作用,有3个衍生物对大肠杆菌具有一定的抑制作用;分子对接结果显示,5个高抑菌活性衍生物与G-6-P合酶均能较好地结合;分子静电势分析表明,羰基和亚砜基团区域是该类衍生物的活性位点,可以与受体G-6-P合酶发生相互作用。新型异噻唑啉酮衍生物广谱抑菌,其可能的抑菌机制是抑制G-6-P合酶的活性。     

异靛蓝衍生物生物活性的研究进展

异靛蓝是一种重要的双吲哚类天然产物,具有多种生物活性.为了增强异靛蓝的生物活性和水溶性,近年来人们对其结构进行了大量的修饰和改造,合成了一些活性较强的衍生物.对近年来异靛蓝衍生物的生物活性及构效关系研究进行了综述.     

环糊精应用新进展:构筑分子选择性光化学传感器

以环糊精及其衍生物为主体分子 ,可设计合成分子选择性光化学传感器。本文概述了环糊精及其衍生物在显色型分子识别检测器、荧光传感器及光纤传感器中的应用。     

Molecular Structures,Vibrational Spectra,Electronic Properties,and Molecular Docking of Two Pyrazoline Derivatives Containing 1-Carboxamide and 1-Carbothioamide: A Comparative Study

Pyrazolines derivatives are nitrogen-containing heterocyclic compound, which exhibit the broad spectrum of biological activities such as antibacterial, antifungal, antiprotozoal, and anti-inflammatory. The optimized geometry, frequency, and intensity of vibrational bands of these compounds are obtained by the density function theory (DFT) using 6–31+G(d,p) basis set. The scaled harmonic vibrational frequencies have been compared with experimental Fourier transform infrared spectroscopy (FTIR) values and found to be in good agreement. The electronic properties of these molecules are discussed with the help of highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), and molecular electrostatic potential (MESP) surfaces, and a number of electronic and thermodynamic parameters are calculated, which are closely related to their chemical reactivity and reaction path. We also notice that pyrazoline derivatives show biological activity for preventing dyskinesia. This study may provide a further investigation on pyrazolines derivatives for pharmacological importance.     

靛玉红类衍生物的三维定量构效关系研究

采用比较分子场方法(CoMFA)对16个靛玉红类衍生物进行三维定量构效关系(3D-QSAR)研究,探讨靛玉红类衍生物的抗癌活性与其结构的关系。建立了3D-QSAR的CoMFA模型,得到了非交叉验证相关系数r2=0.987,标准偏差SD=2.141,统计方差比F=117.136,交叉验证相关系数q2=0.496。该模型合理、可信,具有一定的预测能力,表明改变取代基R1基团的体积才是提高靛玉红类衍生物抗癌活性的主要途径,为开发活性更好的抗癌药物提供一定的理论参考。     

Pharmacological Classification and Activity Evaluation of Furan and Thiophene Amide Derivatives Applying Semi-Empirical ab initio Molecular Modeling Methods

Pharmacological and physicochemical classification of the furan and thiophene amide derivatives by multiple regression analysis and partial least square (PLS) based on semi-empirical ab initio molecular modeling studies and high-performance liquid chromatography (HPLC) retention data is proposed. Structural parameters obtained from the PCM (Polarizable Continuum Model) method and the literature values of biological activity (antiproliferative for the A431 cells) expressed as LD(50) of the examined furan and thiophene derivatives was used to search for relationships. It was tested how variable molecular modeling conditions considered together, with or without HPLC retention data, allow evaluation of the structural recognition of furan and thiophene derivatives with respect to their pharmacological properties.     

Molecular Docking Studies and Biological Evaluation of Berberine–Benzothiazole Derivatives as an Anti-Influenza Agent via Blocking of Neuraminidase

In this study, we have introduced newly synthesized substituted benzothiazole based berberine derivatives that have been analyzed for their in vitro and in silico biological properties. The activity towards various kinds of influenza virus strains by employing the cytopathic effect (CPE) and sulforhodamine B (SRB) assay. Several berberine–benzothiazole derivatives (BBDs), such as BBD1, BBD3, BBD4, BBD5, BBD7, and BBD11, demonstrated interesting anti-influenza virus activity on influenza A viruses (A/PR/8/34, A/Vic/3/75) and influenza B viral (B/Lee/40, and B/Maryland/1/59) strain, respectively. Furthermore, by testing neuraminidase activity (NA) with the neuraminidase assay kit, it was identified that BBD7 has potent neuraminidase activity. The molecular docking analysis further suggests that the BBD1–BBD14 compounds’ antiviral activity may be because of interaction with residues of NA, and the same as in oseltamivir.     

A New N-Substituted 1H-Isoindole-1,3(2H)-Dione Derivative—Synthesis,Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking

Isoindoline-1,3-dione derivatives constitute an important group of medicinal substances. In this study, nine new 1H-isoindole-1,3(2H)-dione derivatives and five potential pharmacophores were obtained in good yield (47.24–92.91%). The structure of the new imides was confirmed by the methods of elemental and spectral analysis: FT–IR, H NMR, and MS. Based on the obtained results of ESI–MS the probable path of the molecules decay and the hypothetical structure of the resulting pseudo-molecular ions have been proposed. The physicochemical properties of the new phthalimides were determined on the basis of Lipiński’s rule. The biological properties were determined in terms of their cyclooxygenase (COX) inhibitory activity. Three compounds showed greater inhibition of COX-2, three compounds inhibited COX-1 more strongly than the reference compound meloxicam. From the obtained results, the affinity ratio COX-2/COX-1 was calculated. Two compounds had a value greater than that of meloxicam. All tested compounds showed oxidative or nitrosan stress (ROS and RNS) scavenging activity. The degree of chromatin relaxation outside the cell nucleus was lower than the control after incubation with all test compounds. The newly synthesized phthalimide derivatives showed no cytotoxic activity in the concentration range studied (10–90 µM). A molecular docking study was used to determined interactions inside the active site of cyclooxygenases.     

In Vitro and In Silico Evaluation of New 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-d]pyridazinone as Promising Cyclooxygenase Inhibitors

Since long-term use of classic NSAIDs can cause severe side effects related mainly to the gastroduodenal tract, discovery of novel cyclooxygenase inhibitors with a safe gastric profile still remains a crucial challenge. Based on the most recent literature data and previous own studies, we decided to modify the structure of already reported 1,3,4-oxadiazole based derivatives of pyrrolo[3,4-d]pyridazinone in order to obtain effective COX inhibitors. Herein we present the synthesis, biological evaluation and molecular docking studies of 12 novel compounds with disubstituted arylpiperazine pharmacophore linked in a different way with 1,3,4-oxadiazole ring. None of the obtained molecules show cytotoxicity on NHDF and THP-1 cell lines and, therefore, all were qualified for further investigation. In vitro cyclooxygenase inhibition assay revealed almost equal activity of new derivatives towards both COX-1 and COX-2 isoenzymes. Moreover, all compounds inhibit COX-2 isoform better than Meloxicam which was used as reference. Anti-inflammatory activity was confirmed in biological assays according to which title molecules are able to reduce induced inflammation within cells. Molecular docking studies were performed to describe the binding mode of new structures to cyclooxygenase. Investigated derivatives take place in the active site of COX, very similar to Meloxicam. For some compounds, promising druglikeness was calculated using in silico predictions.     

含腙类结构化合物生物活性研究进展

含腙类结构的化合物具有杀虫、杀菌、除草等广泛生物活性,在新农药创制中占有重要地位.根据农药用途进行分类,对其生物活性进行了介绍,并对其发展前景作进一步展望.     

A Study on the Effect of the Substituent against PAK4 Inhibition Using In Silico Methods

The intrinsic inductive properties of atoms or functional groups depend on the chemical properties of either electron-withdrawing groups (EWGs) or electron-donating groups (EDGs). This study aimed to evaluate in silico methods to determine whether changes in chemical properties of the compound by single atomic substitution affect the biological activity of target proteins and whether the results depend on the properties of the functional groups. We found an imidazo[4,5-b]pyridine-based PAK4 inhibitor, compound 1, as an initial hit compound with the well-defined binding mode for PAK4. In this study, we used both experimental and in silico methods to investigate the effect of atomic substitution on biological activity to optimize the initial hit compound. In biological assays, in the case of EWG, as the size of the halogen atom became smaller and the electronegativity increased, the biological activity IC₅₀ value ranged from 5150 nM to inactive; in the case of EDG, biological activity was inactive. Furthermore, we analyzed the interactions of PAK4 with compounds, focusing on the hinge region residues, L398 and E399, and gatekeeper residues, M395 and K350, of the PAK4 protein using molecular docking studies and fragment molecular orbital (FMO) methods to determine the differences between the effect of EWG and EDG on the activity of target proteins. These results of the docking score and binding energy did not explain the differences in biological activity. However, the pair-interaction energy obtained from the results of the FMO method indicated that there was a difference in the interaction energy between the EWG and EDG in the hinge region residues, L398 and E399, as well as in M395 and K350. The two groups with different properties exhibited opposite electrostatic energy and charge transfer energy between L398 and E399. Additionally, we investigated the electron distribution of the parts interacting with the hinge region by visualizing the molecular electrostatic potential (MEP) surface of the compounds. In conclusion, we described the properties of functional groups that affect biological activity using an in silico method, FMO.     

姜黄素结构修饰的研究进展

对姜黄素衍生物类药物的结构修饰进行归类,探讨了姜黄素衍生物的生物活性与化学结构的关系,分析了姜黄素衍生物中化学基团对生物活性的影响,为以后合成具有高效专一的生物活性姜黄素衍生物提供依据。     

吡唑啉类化合物生物活性及研究进展

吡唑啉衍生物具有抗菌、抗炎、抗变形虫、抗肿瘤等生物活性,在医药与农药创制中占有重要地位。根据吡唑啉衍生物在医药与农药中的用途进行分类,对其生物活性进行介绍,并对其发展前景作进一步展望。