A search for kinase inhibitors and antibacterial agents: bromopyrrolo-2-aminoimidazoles from a deep-water Great Australian Bight sponge, Axinella sp.

Biological screening of a deep-water Great Australian Bight marine sponge, Axinella sp., detected inhibition against the neurodegenerative disease kinase targets CDK5/p25, CK1δ, and GSK3β, as well as significant levels of antibacterial activity. Chemical fractionation returned 18 secondary metabolites identified by detailed spectroscopic analysis as three new bromopyrrolo-2-aminoimidazoles, 14-O-sulfate massadine (1), 14-O-methyl massadine (2), and 3-O-methyl massadine chloride (3), together with the known metabolites massadine chloride (4), massadine (5), stylissadine B (6), axinellamines A-C (7-9), hymenin (10), stevensine (also known as odiline) (11), tauroacidin A (12), hymenidin (13), taurodispacamide A (14), oroidin (15), debromohymenialdisine (16), hymenialdisine (17), and aldisin (18). Armed with this focused natural product chemical diversity library, we re-established that 16 and 17 were nM kinase inhibitors, and determined that 3, 6, and 12-15 were sub μM antibacterials.     

Evaluation on bioactivities of triterpenes from Bergenia emeiensis

Bergenia emeiensis is a traditional folk medicine in China. Most studies are focusing on the bioactivity of bergenin, neglecting other compounds. Therefore, in this present work, the antioxidant, antibacterial and anticancer abilities of triterpenes from B. emeiensis rhizomes (TBE) were comprehensively evaluated. The results showed that TBE could well scavenge DPPH with a lower EC50 of 0.29 mg/mL and could improve the cell viability of CHO cells against H₂O₂ induced cell death. Additionally, TBE also enhanced the resistance of C. elegans under thermal stress, exhibiting a strong antioxidant potential in vivo. Moreover, TBE showed a certain antibacterial ability on five kind strains such as Pseudomonas aeruginosa while TBE could not significantly inhibit the growth of plant pathogenic fungi. Furthermore, TBE possessed an excellent suppression ability on the proliferation of cancer cells especially Hela and Hep G2 cells with an IC50 of 41.79 μg/mL and 48.62 μg/mL at 48 h, respectively. After fractionally extracted with petroleum ether, ethyl acetate and ethanol, ethanol phase (EP) contained the most triterpenes, followed by ethyl acetate phase (EAP) and petroleum ether phase (PEP). Besides, EP and EAP exhibited a strong antioxidant capacity and also inhibited the proliferation of Hela and Hep G2 cells with the effect of pro-oxidation by inducing a high level of ROS and decreasing mitochondrial membrane potential, thus causing oxidative stress then inducing cell apoptosis. Therefore, these outcomes indicated the triterpenes from B. emeiensis possessed a strong antioxidant ability and an anticancer effect, thus making B. emeiensis become a promising potential alternative in pharmacological field.     

概念图在化学教学中应用的中外研究对比——基于CiteSpace的知识图谱可视化分析

以CiteSpace为工具,对2009-2018年10年间概念图在化学教学中应用的中外研究文献进行可视化的对比分析.研究表明:与国外研究相比,在应用范围上,国内缺少概念图在大学化学教学中应用的相关研究;在研究内容上,国内学者应加强概念图培养学生高阶思维能力及创造力的研究;从评估方式看,国内较少采用定性和定量相结合的评估...     

层层静电自组装构建壳聚糖/肝素抗菌多层膜的研究

聚对苯二甲酸乙二醇酯（PET）由于其突出的机械性能和良好的生物相容性而广泛用作心血管的植入材料,但是植入内置医用材料时会发生感染,这直接导致了较高的发病率和死亡率,传统的抗感染的表面设计包括与抗菌药物机械共混和表面化学接枝抗菌药物等,但是采用简单的机械共混方式制备的材料中药物负载可控性差,表面化学接枝涉及步骤繁杂的合成工艺很难在具有复杂体型结构的医用装置上实现,因此寻求一种简单的面对装置的表面修饰手段成为医用装置抗感染表面设计的关键性问题。     

蜂毒肽C末端片段的反序肽的抗菌活性和溶血活性

设计并合成了具有不同碱性氨基酸残基数和不同疏水性片段链长的基于Mel(12~26)的系列反序肽类似物.结果表明,反序肽的正电荷和疏水性对于抑菌活性都很重要,N端至少保留3个碱性氨基酸(正电荷>4)和C端的疏水性片段的链长至少为8个氨基酸残基的类似物具有较高的抑菌活性,具有较大的抑菌活性的最小反序肽类似物为具有11个氨基酸残基的RetroMel(13~23).这些反序肽的溶血活性都很小.     

Synthesis of Thio Analogues of Quinolone Antibacterials

A facile and rapid synthesis of thio compounds, analogues to ciprofloxacin, and norfloxacin is described.     

新型1,2,3-三唑类化合物的合成及抗菌构效关系

根据活性基团拼接原理, 以4-取代-苯胺为原料, 经重氮化、 关环和缩合反应合成了17个化合物1-(4-取代苯基)-5-取代苯基亚氨基-4-取代-1,2,3-三唑(7a~7c和13a~13d)和1-(4-取代苯基)-5-取代苄基氨基-4-取代-1,2,3-三唑(5a~5c, 10a~10c和14a~14d), 其中化合物5a~5c, 7b, 7c, 10a, 10c, 13b~13d和14b~14c为新化合物, 对所制备化合物的结构进行了表征. 生物活性测试结果表明, 所有化合物均表现出一定的抑菌活性, 对大肠杆菌的抑菌活性均优于氟康唑; 化合物7a和10c对金黄色葡萄球菌的抑制活性明显优于氟康唑; 而化合物13a和13d则对白色念球菌表现出良好的抑制活性, 与三氯生相当.     

Synthesis and Biological Evaluation of Novel Tetracyclic Benzothiazepines

6-Arylidene-2,3-dimethyl-6,7,8,9-tetrahydro-benzocyclohepten-5-one 2a–l were obtained by the condensation of 2,3-dimethyl/3-methyl benzocyclohepten-5-one 1 with appropriate aromatic aldehydes, and upon condensation with 2-aminothiophenol in ethyl alcohol yielded 1,5-benzothiazepine derivatives 3a–l, respectively. Compounds 3d and 3h were found to possess antimicrobial activity when tested against B. Subtilis. Compounds 3i and 3j were found to possess moderate anti-inflammatory activity. Compound 3b was found to possess comparable antifungal activity when compared to clotrimazole against Trichomonas species.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Petra,Osiris, and Molinspiration Together as a Guide in Drug Design: Predictions and Correlation Structure/Antibacterial Activity Relationships of New N-Sulfonyl Monocyclic β-Lactams

We report in this article the design and calculated molecular properties of 18 new mono-cyclic β-lactams 4–21, on the basis of one hypothetical antibacterial pharmacophore structure designed to interact with both of Gram-positive bacteria and Gram-negative bacteria. The in vitro biological evaluation of these compounds allowed us to point out new potential non-nucleoside hits, with MIC values in the range of 2–8 μg/mL active against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. A correlation structure/antibacterial activities relationship of these monocyclic β-lactams is described.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Impact of Geometric Parameters,Charge, and Lipophilicity on Bioactivity of Armed Quinoxaline,Benzothiaole, and Benzothiazine: Pom Analyses of Antibacterial and Antifungal Activity

Abstract

A series of four different armed heterocyclic candidates; 1-(2-methyl-2,3-dihydro-1,3-benzothiazol-2-yl)acetone (2), 1-(3-methyl-4H-1,4-benzothiazin-2-yl)ethanone (3), 2-[(2-aminophenyl)dithio]aniline (4), and 3-hydroxy-3-methyl-4-(3-methyl-2-quinoxalinyl)-2-butanone (5) have been prepared and their microbial activities were evaluated. A correlation of the structure and activities relationships of these compounds with respect to molecular modeling, Lipinski Rule of Five, drug likeness, toxicity profiles, and other physico-chemical properties of drugs are described and verified experimentally.