Cytotoxic Alangium alkaloids from Alangium longiflorum

Seven alkaloids (1-7) were isolated from the stem bark of Alangium longiflorum. Compound 1, (-)-10-O-demethylisocephaeline, was isolated for the first time as a naturally occurring product from a plant source. All structures were elucidated by detailed spectroscopic analysis. Biological evaluation showed that 2, 10-O-demethylcephaeline, exhibited potent cytotoxic activity against human lung carcinoma (A549) and breast adenocarcinoma (MCF-7) with ED(50) values of 0.013 and 0.062 microM, respectively. The stereoisomer 1 was less potent than 2, and related compounds with different hydroxy/methoxy substitution patterns were also less potent or inactive. Thus, compound 2 merits attention as a cytotoxic lead for further study.     

1,2,3-Triazole-nimesulide hybrid: Their design,synthesis and evaluation as potential anticancer agents

A new hybrid template has been designed by integrating the structural features of nimesulide and the 1,2,3-triazole moiety in a single molecular entity at the same time eliminating the problematic nitro group of nimesulide. The template has been used for the generation of a library of molecules as potential anticancer agents. A mild and greener CuAAC approach has been used to synthesize these compounds via the reaction of 4-azido derivative of nimesulide and terminal alkynes in water. Three of these compounds showed promising growth inhibition (IC₅₀ ～6–10 μM) of A549, HepG2, HeLa and DU145 cancer cell lines but no significant effects on HEK293 cell line. They also inhibited PDE4B in vitro (60–70% at 10 μM) that was supported by the docking studies (PLP score 87–94) in silico.     

Marine drugs--macrolactins

The increasing demands for new lead compounds in pharmaceutical and agrochemical industries have driven scientists to search for new bioactive natural products. Marine microorganisms are rich sources of novel, bioactive secondary metabolites, and have attracted much attention of chemists, pharmacologists, and molecular biologists. This mini-review mainly focuses on macrolactins, a group of 24-membered lactone marine natural products, aiming at giving an overview on their sources, structures, biological activities, as well as their potential medical applications.     

薇甘菊提取物对红脉穗螟的产卵忌避及杀卵作用

【目的】探讨入侵杂草薇甘菊Mikania micrantha对棕榈害虫红脉穗螟Tirathaba rufivena的产卵忌避活性。【方法】采用室内生物测定法,研究薇甘菊不同溶剂提取物对红脉穗螟的产卵忌避作用和杀卵活性。【结果】产卵忌避试验结果表明,薇甘菊各提取物中,以正己烷和三氯甲烷提取物对红脉穗螟的产卵忌避效果最好,两者的选择性忌避率分别为43.64%和44.20%,非选择性忌避率分别为51.60%和59.20%。对卵孵化率的影响显示,各溶剂提取物均对红脉穗螟具有一定的杀卵活性,其中三氯甲烷提取物对卵孵化率的影响最大,校正孵化率最低,仅为53.39%,而且三氯甲烷提取物引起的1龄幼虫的死亡率最高,可达42.64%。在薇甘菊三氯甲烷提取物的不同溶剂萃取物中,正丁醇萃取物对红脉穗螟的产卵忌避和杀卵活性均显著高于其他溶剂萃取物。【结论】薇甘菊提取物具有一定的产卵忌避和杀卵活性,具有用于红脉穗螟的生态防控的潜力。     

Extended N6 substitution of rigid C2-arylethynyl nucleosides for exploring the role of extracellular loops in ligand recognition at the A3 adenosine receptor

2-Arylethynyl-(N)-methanocarba adenosine 5′-methyluronamides containing rigid N⁶-(trans-2-phenylcyclopropyl) and 2-phenylethynyl groups were synthesized as agonists for probing structural features of the A₃ adenosine receptor (AR). Radioligand binding confirmed A₃AR selectivity and N⁶-1S,2R stereoselectivity for one diastereomeric pair. The environment of receptor-bound, conformationally constrained N⁶ groups was explored by docking to an A₃AR homology model, indicating specific hydrophobic interactions with the second extracellular loop able to modulate the affinity profile. 2-Pyridylethynyl derivative 18 was administered orally in mice to reduce chronic neuropathic pain in the chronic constriction injury model.     

Colorimetric estimation of human glucose level using γ-Fe2O3 nanoparticles: An easily recoverable effective mimic peroxidase

This article reports simple, green and efficient synthesis of γ-Fe₂O₃ nanoparticles (NPs) (maghemite) through single-source precursor approach for colorimetric estimation of human glucose level. The γ-Fe₂O₃ NPs, having cubic morphology with an average particle size of 30 nm, exhibited effective peroxidase-like activity through the catalytic oxidation of peroxidase substrate 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H₂O₂ producing a blue-colored solution. On the basis of this colored-reaction, we have developed a simple, cheap, highly sensitive and selective colorimetric method for estimation of glucose using γ-Fe₂O₃/TMB/glucose–glucose oxidase (GOx) system in the linear range from 1 to 80 μM with detection limit of 0.21 μM. The proposed glucose sensor displays faster response, good stability, reproducibility and anti-interference ability. Based on this simple reaction process, human blood and urine glucose level can be monitored conveniently.     

Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition

Experimental evidence suggests that the maintenance of an item in working memory is achieved through persistent activity in selective neural assemblies of the cortex. To understand the mechanisms underlying this phenomenon, it is essential to investigate how persistent activity is affected by external inputs or neuromodulation. We have addressed these questions using a recurrent network model of object working memory. Recurrence is dominated by inhibition, although persistent activity is generated through recurrent excitation in small subsets of excitatory neurons.Our main findings are as follows. (1) Because of the strong feedback inhibition, persistent activity shows an inverted U shape as a function of increased external drive to the network. (2) A transient external excitation can switch off a network from a selective persistent state to its spontaneous state. (3) The maintenance of the sample stimulus in working memory is not affected by intervening stimuli (distractors) during the delay period, provided the stimulation intensity is not large. On the other hand, if stimulation intensity is large enough, distractors disrupt sample-related persistent activity, and the network is able to maintain a memory only of the last shown stimulus. (4) A concerted modulation of GABA _A and NMDA conductances leads to a decrease of spontaneous activity but an increase of persistent activity; the enhanced signal-to-noise ratio is shown to increase the resistance of the network to distractors. (5) Two mechanisms are identified that produce an inverted U shaped dependence of persistent activity on modulation. The present study therefore points to several mechanisms that enhance the signal-to-noise ratio in working memory states. These mechanisms could be implemented in the prefrontal cortex by dopaminergic projections from the midbrain.