Sinapic acid derivatives in microwave-pretreated rapeseeds and minor components in oils

Microwave pretreatment has been considered to improve the quality of rapeseed oil for canolol generation. Canolol is assumed to be formed by the decarboxylation of sinapic acid (SA). In this work, sinapic acid derivatives in 39 microwave-pretreated rapeseeds and their roles in the enhanced oxidative stability of rapeseed oils were investigated. The average contents of sinapic acid derivatives in rapeseeds, including (from high to low) sinapine, sinapoyl glucoside (SG), disinapoyl gentiobioside (DSG), quercetin-sinapoyl-di-hexosepentose (QSDG), sinapoyl malate (SM), disinapoyl glucoside (DDSG) and SA, were determined. After microwave pretreatment, the canolol content in rapeseed increased from nil to 6.16–76.1 mg/100 g, while sinapic acid derivatives contents decreased. The degradation rates of SG, DDSG, DSG, SM, SA and sinapine were 59.1%, 40.2%, 33.7%, 27.4%, 14.4% and 11.3%, respectively. There was no correlation relationship between sinapine and canolol. However, SG, DSG, SM and DDSG were regarded to be the precursor substances of canolol. Additionally, the tocopherols, sterols and canolol contents, along with the induction period (IP) of microwaved rapeseed oil increased by 3.79%, 10.0%, 76.8 times and 38.7%, respectively. There was a significant positive correlation between IP and canolol content. These findings clarify the precursor substances of canolol and provide a theoretical support for the development and utilization of canolol.     

Molecular approaches to allergen‐specific immunotherapy: Are we so far from clinical implementation?

Conventional allergen‐specific immunotherapy (AIT), based on administrations of allergen extracts, represents up to now the unique protocol for the desensitization of allergic patients. Whereas the effectiveness of AIT was evidenced for the treatment of allergic rhinitis and allergic asthma, such strategy remains experimental for food allergies up to now. However, important issues are commonly associated with AIT as the quality of natural allergen extracts, the long duration and adverse side‐effects which negatively affect successful desensitization together with the patient compliance. The rapid progression of molecular allergology made possible the quest of safer, shorter and more effective immunotherapeutic approaches. The aim of this review was to provide an update on these different innovative recombinant derivatives including their efficacy but also their limitations. Despite promising preclinical and early clinical studies, the absence of convincing data in large phase III trials precludes so far the translation of these immunotherapeutic candidates into the clinic.     

银杏酸C17:1衍生物增效达托霉素抗粪肠球菌的发现与机制的初步研究

目的 发现有抗菌活性或是增效活性的银杏酸C17:1衍生物。方法 以银杏酸C17:1为底物，利用一些基团取代苯环上的羧基从而获得银杏酸C17:1衍生物，棋盘法设计试验，测定银杏酸C17:1及其衍生物联合抗生素的增效作用，通过测定Zeta电位、ROS、NPN吸收来探究增效机制。结果 银杏酸C17:1衍生物Ⅱ与达托霉素联合抗粪肠球菌的部分抑菌浓度指数(FICIs)为0.125~0.25，具有明显的协同效应，不仅能产生较高的活性氧，而且能在一定程度改变细胞膜的通透性。结论 银杏酸衍生物Ⅱ对达托霉素体外抗耐药株具有较好的增效作用，可能和ROS的激增以及膜通透性的改变有关。     

Investigation of the antibacterial and antifungal activity of thiolated naphthoquinones

The WHO has stated that antibiotic resistance is escalating to perilously high levels globally and that traditional therapies of antimicrobial drugs are futile against infections caused by resistant microorganisms. Novel antimicrobial drugs are therefore required. We report in this study on the inhibitory activity of the 1,4-naphthoquinone-2,3-bis-sulfides and 1,4-naphthoquinone sulfides against two bacteria and a fungus to determine their antimicrobial properties. The 1,4-naphthoquinone sulfides have potent activity with a minimum inhibitory concentration (MIC) of 7.8 μg/mL against Staphylococcus aureus (Gram +ve), an MIC of 23.4 μg/mL against the fungus, Candida albicans, which was better than that of Amphotericin B (MIC = 31.3 μg/mL), and against Escherichia coli (Gram −ve) an MIC of 31.3 μg/mL was obtained. The 1,4-naphthoquinone had an MIC of 11.7 μg/mL against S. aureus and the 1,4-naphthohydroquinone also had the same activity against E. coli.

Synthesis and antiproliferative activity of new mycophenolic acid conjugates with adenosine derivatives

New conjugates of mycophenolic acid (MPA) and adenosine derivatives were synthesized and assessed as potential immunosuppressants on Jurkat cell line and peripheral blood mononuclear cells (PBMC) from healthy donors. As compared to MPA, all compounds were found to be more active against Jurkat cell line. The antiproliferative activities were compared with MPA and adenosine, in both 2′,3′-O-isopropylidene protected and free hydroxyl groups possessing forms. The obtained results were also discussed in terms of selectivity index, defined as SI = IC₅₀/EC₅₀.     

Design,synthesis, and evaluation of novel cinnamic acid-tryptamine hybrid for inhibition of acetylcholinesterase and butyrylcholinesterase

BackgroundAcetylcholine deficiencies in hippocampus and cortex, aggregation of β-amyloid, and β-secretase over activity have been introduced as main reasons in pathogenesis of Alzheimer’s disease.MethodsColorimetric Ellman’s method was used for determination of IC₅₀ value in AChE and BChE inhibitory activity. The kinetic studies, neuroprotective and β-secretase inhibitory activities, evaluation of inhibitory potency on β-amyloid (Aβ) aggregations induced by AChE, and docking study were performed for prediction of the mechanism of action.Result and discussionA new series of cinnamic acids-tryptamine hybrid was designed, synthesized, and evaluated as dual cholinesterase inhibitors. These compounds demonstrated in-vitro inhibitory activities against acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE). Among of these synthesized compounds, (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(3,4-dimethoxyphenyl)acrylamide (5q) demonstrated the most potent AChE inhibitory activity (IC₅₀ = 11.51 μM) and (E)-N-(2-(1H-indol-3-yl)ethyl)-3-(2-chlorophenyl)acrylamide (5b) were the best anti-BChE (IC₅₀ = 1.95 μM) compounds. In addition, the molecular modeling and kinetic studies depicted 5q and 5b were mixed type inhibitor and bound with both the peripheral anionic site (PAS) and catalytic sites (CAS) of AChE and BChE. Moreover, compound 5q showed mild neuroprotective in PC12 cell line and weak β-secretase inhibitory activities. This compound also inhibited aggregation of β-amyloid (Aβ) in self-induced peptide aggregation test at concentration of 10 μM.ConclusionIt is worth noting that both the kinetic study and the molecular modeling of 5q and 5b depicted that these compounds simultaneously interacted with both the catalytic active site and the peripheral anionic site of AChE and BChE. These findings match with those resulted data from the enzyme inhibition assay. Graphical abstractOpen in a separate windowA new series of cinnamic-derived acids-tryptamine hybrid derivatives were designed, synthesized and evaluated as butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) inhibitors and neuroprotective agents. Compound 5b and 5q, as the more potent compounds, interacted with both the peripheral site and the choline binding site having mixed type inhibition. Results suggested that derivatives have a therapeutic potential for the treatment of AD.Electronic supplementary materialThe online version of this article (10.1007/s40199-020-00346-9) contains supplementary material, which is available to authorized users.     

Synthesis and biological evaluation of phloroglucinol derivatives possessing α‐glycosidase,acetylcholinesterase, butyrylcholinesterase,carbonic anhydrase inhibitory activity

A series of novel phloroglucinol derivatives were designed, synthesized, characterized spectroscopically and tested for their inhibitory activity against selected metabolic enzymes, including α‐glycosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCA I and II). These compounds displayed nanomolar inhibition levels and showed K_i values of 1.14–3.92 nM against AChE, 0.24–1.64 nM against BChE, 6.73–51.10 nM against α‐glycosidase, 1.80–5.10 nM against hCA I, and 1.14–5.45 nM against hCA II.

     

Design,synthesis, biological evaluations,molecular docking,and in vivo studies of novel phthalimide analogs

A series of novel phthalimide analogs containing an indole or brominated indole moiety were synthesized and their antimicrobial activity was evaluated. Compound 8 showed a broad spectrum activity, revealing 53–67% of erythromycin activity on the tested bacteria and 60–70% of miconazole activity on the tested fungi. Anticancer activity was evaluated on the cell lines HepG2, MCF‐7, A549, H1299, and Caco2. The results revealed that the new phthalimide analog 8 has broad‐spectrum anticancer activity toward all the tested cancer cell lines, followed by compound 11 , which showed good activity toward all the tested cell lines except for MCF‐7. The ability of the promising analogs 5 , 8 , and 11 to bind to topoisomerase II DNA gyrase was investigated. Caspase‐3 activation and Bcl‐2 assay of the best active derivatives 8 , 11 in addition to compound 5 were evaluated. The antifibrotic activity was studied in an in vivo model and the histopathological studies revealed that treatment with the new compound 8 improved the fibrotic liver tissues to normality.

     

红景天苷衍生物的合成及其抗疲劳活性研究

目的 设计并合成系列4-取代的新型红景天苷衍生物并研究其抗疲劳作用。方法 通过五乙酰基葡萄糖与不同的4-取代苄基酪醇,经过糖苷化、脱乙酰基合成红景天苷衍生物;采用小鼠负重游泳为实验模型,通过观察测定小鼠的负重游泳时间研究合成衍生物的抗疲劳作用。结果 合成了10个新型红景天苷衍生物;小鼠负重游泳实验显示：阳性对照组（红景天苷）和3a-1组（苯乙基-β-D-葡萄糖苷）的小鼠游泳时间明显高于空白对照组（P<0.05）,差异有统计学意义;其余组均与空白对照组小鼠负重游泳时间相近,差异无统计学意义。结论 本实验设计的红景天苷衍生物合成方法简便、可行;红景天苷及其衍生物苯环上的4位羟基可能与其抗疲劳活性密切相关。     

聚乙二醇衍生物及其蛋白药物修饰研究进展

聚乙二醇及其衍生物因其出色的亲水性、生物相容性、生物学惰性等特性而被广泛应用于蛋白药物修饰,其修饰可有效降低蛋白药物的免疫原性并延长体内半衰期。聚乙二醇衍生物的发展经历了第一代随机修饰,第二代特异性和功能性修饰,以及第三代分支型结构的应用。其应用也从简单的药物修饰扩展到生物传感、药物传输等方面。