Chemical profile by LC–MS/MS,GC/MS and antioxidant activities of the essential oils and crude extracts of two Euphorbia species

In this study, it was aimed to investigate the chemical composition and antioxidant activities of two Euphorbia species. The major component of the fatty acid compositions obtained from the petroleum ether extracts was identified as palmitic acid for Euphorbia gaillardotii and Euphorbia macroclada. The main constituents of the essential oils were identified as arachidic acid for E. gaillardotii and tetratetracontane for E. macroclada. Among the 27 studied compounds, hesperidin, rutin, hyperoside and quinic, malic, gallic and tannic acids were found to be the most abundant compounds in the two Euphorbia species. The methanol extracts of E. gaillardotii and E. macroclada showed strong antioxidant activity in all tested methods. Particularly, IC₅₀ values of E. macroclada methanol extract that was the richest in terms of total phenolic-flavonoid contents were found to be lower than α-tocopherol and butylated hydroxytoluene in β-carotene bleaching, 2,2-diphenyl-1-picrylhydrazyl free and ABTS cation radical scavenging methods.     

Design and Synthesis of High‐Affinity Dimeric Inhibitors Targeting the Interactions between Gephyrin and Inhibitory Neurotransmitter Receptors

Gephyrin is the central scaffolding protein for inhibitory neurotransmitter receptors in the brain. Here we describe the development of dimeric peptides that inhibit the interaction between gephyrin and these receptors, a process which is fundamental to numerous synaptic functions and diseases of the brain. We first identified receptor‐derived minimal gephyrin‐binding peptides that displayed exclusive binding towards native gephyrin from brain lysates. We then designed and synthesized a series of dimeric ligands, which led to a remarkable 1220‐fold enhancement of the gephyrin affinity (K_D=6.8 nM ). In X‐ray crystal structures we visualized the simultaneous dimer‐to‐dimer binding in atomic detail, revealing compound‐specific binding modes. Thus, we defined the molecular basis of the affinity‐enhancing effect of multivalent gephyrin inhibitors and provide conceptually novel compounds with therapeutic potential, which will allow further elucidation of the gephyrin–receptor interplay.     

Design and Enantioselective Synthesis of Cashmeran Odorants by Using “Enol Catalysis”

Novel Cashmeran odorants were designed by molecular modeling. Their short syntheses involve a novel asymmetric Brønsted acid catalyzed Michael addition of unactivated α‐substituted ketones. This key transformation was realized by utilizing a new type of enol activation catalysis and affords different cyclic ketones bearing α‐quaternary stereocenters in good to excellent yields and with high enantioselectivity. Subsequent McMurry coupling and Saegusa–Ito oxidation furnished the enantiopure target odorants, one enantiomer of which indeed possesses the typical olfactory aspects of Cashmeran.     

Identification of Structure–Activity Relationships from Screening a Structurally Compact DNA‐Encoded Chemical Library

Methods for the rapid and inexpensive discovery of hit compounds are essential for pharmaceutical research and DNA‐encoded chemical libraries represent promising tools for this purpose. We here report on the design and synthesis of DAL‐100K, a DNA‐encoded chemical library containing 103 200 structurally compact compounds. Affinity screening experiments and DNA‐sequencing analysis provided ligands with nanomolar affinities to several proteins, including prostate‐specific membrane antigen and tankyrase 1. Correlations of sequence counts with binding affinities and potencies of enzyme inhibition were observed and enabled the identification of structural features critical for activity. These results indicate that libraries of this type represent a useful source of small‐molecule binders for target proteins of pharmaceutical interest and information on structural features important for binding.     

Phosphodiester Cleavage Promoted by an Asymmetric Di­nuclear Zinc Complex: Synthesis,Structure, and Catalytic ­Activity

The dinuclear Zn^II complex [Zn₂L(DNBA)₂]BPh₄ · EtOH ( 1 ) (DNBA = 3,5‐dinitrobenzonic acid) with an asymmetric dinuclear ligand, N‐4‐methyl‐homopiperazine‐N′‐[N‐(2‐pyridylmethyl)‐N‐2‐(2‐pyridylethyl)amine]‐1,3‐diamino‐propan‐2‐ol (HL), was synthesized and characterized. Single crystal X‐ray crystallographic analysis shows that the coordination around the two Zn^II ions in 1 is significantly asymmetric, and the distance between both atoms is 3.426 Å, which is close to the Zn···Zn distance in related natural dinuclear metalloenzymes. Phosphodiesterase activity of Zn₂L in situ formed from a 2:1 mixture of Zn²⁺ ion and HL was investigated using bis(4‐nitrophenyl) phosphate (BNPP) as substrate. The pH dependence of the BNPP cleavage in aqueous buffer media reveals a bell‐shaped pH‐k_obs profile with an optimum at about pH 7.9, which is parallel to the formation of the dinuclear species Zn₂L‐OH obtained from the potentiometric titration. The catalytic rate constant (k_cat) is 6.30 × 10^–4 s^–1 at pH 7.9 and 25 °C, which is approx. 10⁸‐fold higher than that of the uncatalyzed reaction. The homopiperazine bound deprotonated Zn‐OH group is responsible for the hydrolysis reaction. The possible mechanism for the BNPP cleavage promoted by Zn₂L is proposed on the basis of kinetic and spectral analysis.     

Cyclometalated Iridium(III) Complexes Containing Semicarbazone Ligands: Synthesis,Characterization, Photophysical and Biological Studies

The synthesis, crystal structure, photophysical properties, and biological activity of the novel bis‐cyclometalated complexes [Ir(ptpy)₂(vnsc)] ( 2 ) and [Ir(ptpy)₂(acsc)] ( 3 ) [ptpy = 2‐(p‐tolyl)pyridinato, vnsc = vanillin semicarbazone, acsc = acetone semicarbazone] are described. The new compounds were prepared by the reaction of [{Ir(μ‐Cl)(ptpy)₂}₂] ( 1 ) with the corresponding semicarbazone ligands under basic conditions. The molecular structure of compound 3 was confirmed by a single‐crystal X‐ray diffraction study. The complex crystallized from chloroform as a mono‐ solvate in the orthorhombic space group Pcab with eight molecules in the unit cell.     

环己基(三甲基硅基亚甲基)锡二芳香酸酯的合成、结构和抗癌活性

采用环己基(三甲基硅基亚甲基)二氯化锡和芳香酸(物质的量比1:2)在三乙胺存在下,合成了8种新的混合二烃基锡化合物环己基(三甲基硅基亚甲基)锡二芳香酸酯。 通过IR、¹H NMR、¹³C NMR和元素分析等技术手段对它们的结构进行了表征;部分化合物的生物活性测定初步结果表明,它们对肺腺癌细胞(A549)有较好的体外抗癌活性,抑制率均在75%以上。     

An Antibacterial Nonenzymatic Glucose Sensor Composed of Carbon Nanotubes Decorated with Silver Nanoparticles

A glucose sensor composed of silver nanoparticles decorated carbon nanotubes (Ag‐NPs/CNTs) prepared by ion implantation is described. Ag‐NPs with size of 2–4 nm are uniformly distributed in the CNTs after ion implantation. This process provides a strong combination between Ag‐NPs and CNTs and can effectively prevent the Ag‐NPs from aggregation. A linear range of 125 µM to 10 mM towards glucose determination was obtained. The Ag‐NPs/CNTs electrode shows minimal interferences from co‐existence species such as uric acid and ascorbic acid and an antibacterial rate of 94 % towards E. coli.     

Terpenoids from the Stems of Drypetes congestiflora

Two new eremophilane‐type sesquiterpenoids, 1α‐hydroxyeremophila‐6,9,11‐trien‐8‐one ( 1 ), 4α‐hydroxyeremophila‐1,9‐diene‐3,8‐dione ( 2 ), and a new friedelane‐type triterpenoid, friedelane‐3α,16β‐diol ( 4 ), along with six known terpenoids, 3 and 5 – 9 , have been isolated from the stems of Drypetes congestiflora. Their structures and relative configurations were elucidated on the basis of detailed spectroscopic analyses and by comparison of their NMR data with those reported in the literature. All of the compounds, 1 – 9 , were isolated for the first time from this species. Compound 3 exhibited moderate cytotoxic activities against the A549 and B16F10 cell lines.     

Two 2,6‐Dioxabicyclo[3.3.1]nonan‐3‐ones from Phragmanthera capitata (Spreng.) Balle (Loranthaceae)

Phytochemical investigation of the leaves of Phragmanthera capitata collected on Cassia spectabilis tree led to the isolation of two natural lactones, rel‐(1R,5S,7S)‐7‐[2‐(4‐hydroxyphenyl)ethyl]‐2,6‐dioxabicyclo[3.3.1]nonan‐3‐one ( 1 ) and 4‐{2‐[rel‐(1R,3R,5S)‐7‐oxo‐2,6‐dioxabicyclo[3.3.1]non‐3‐yl]ethyl}phenyl 3,4,5‐trihydroxybenzoate ( 2 ) together with the known compounds betulinic acid ( 3 ), dodoneine ( 4 ), quercetin 3‐O‐α‐L ‐rhamnopyranoside ( 5 ), quercetin 3‐O‐α‐L ‐arabinofuranoside ( 6 ), quercetin ( 7 ), betulin ( 8 ), lupeol ( 9 ), and sitosterol ( 10 ). Their structures were established by means of modern spectroscopic techniques, and the relative configuration of compound 1 was confirmed by X‐ray analysis. Compounds 1 and 2 were tested in vitro for their antiplasmodial activity against the Plasmodium falciparum chloroquine sensitive‐strains NF54 and 3D7. Compound 2 exhibited good antiplasmodial activity against both strains with IC₅₀ of 2.4 and 4.9 μM , respectively, while compound 1 was inactive.