4-Connected azabicyclo[5.3.0]decane Smac mimetics-Zn2+ chelators as dual action antitumoral agents

Putative dual action compounds (DACs 3a–d) based on azabicyclo[5.3.0]decane (ABD) Smac mimetic scaffolds linked to Zn²⁺-chelating 2,2′-dipicolylamine (DPA) through their 4 position are reported and characterized. Their synthesis, their target affinity (cIAP1 BIR3, Zn²⁺) in cell-free assays, their pro-apoptotic effects, and their cytotoxicity in tumor cells with varying sensitivity to Smac mimetics are described. A limited influence of Zn²⁺ chelation on in vitro activity of DPA-substituted DACs 3a–d was sometimes perceivable, but did not lead to strong cellular synergistic effects. In particular, the linker connecting DPA with the ABD scaffold seems to influence cellular Zn²⁺-chelation, with longer lipophilic linkers/DAC 3c being the optimal choice.     

Anti-HSV-1, antioxidant and antifouling phenolic compounds from the deep-sea-derived fungus Aspergillus versicolor SCSIO 41502

Chemical investigation of the deep-sea-derived fungus Aspergillus versicolor SCSIO 41502 resulted in the isolation of three new anthraquinones, aspergilols G-I (1–3), one new diphenyl ether, 4-carbglyceryl-3,3′-dihydroxy-5,5′-dimethyldiphenyl ether (4), and one new benzaldehyde derivative, 2,4-dihydroxy-6-(4-methoxy-2-oxopentyl)-3-methylbenzaldehyde (5), along with 23 known phenolic compounds (6–28). The structures of new compounds were elucidated by extensive spectroscopic analysis. The absolute configuration of 3 was established by CD spectrum and the modified Mosher method. Compounds 2, 3 and 9 had evident antiviral activity towards HSV-1 with EC₅₀ values of 4.68, 6.25, and 3.12 μM, respectively. Compounds 15, 18, 20 and 22–24 showed more potent antioxidant activity than l-ascorbic acid with IC₅₀ values of 18.92–52.27 μM towards DPPH radicals. Comparison of the structures and antioxidant activities of 1–28 suggests that the number of phenolic hydroxyl group that can freely rotate can significantly affect the antioxidant activity of phenolic compounds. In addition, 4, 22–24 and 27 had significant antifouling activity against Bugula neritina larval settlement with EC₅₀ values of 1.28, 2.61, 5.48, 1.59, and 3.40 μg/ml, respectively.     

Synthesis and structure–activity relationship studies of phenolic hydroxyl derivatives based on quinoxalinone as aldose reductase inhibitors with antioxidant activity

To enhance aldose reductase (ALR2) inhibition and add antioxidant ability, phenolic hydroxyl was introduced both to the quinoxalinone core and C3 side chain, resulting in a series of derivatives as ALR2 inhibitors. Biological activity tests suggested that most of the derivatives were potent and selective inhibitors with IC₅₀ values ranging from 0.059 to 6.825 μM, and 2-(3-(4-hydroxystyryl)-7-methoxy-2-oxoquinoxalin-1(2H)-yl)acetic acid (6b) was the most active. Particularly, it was encouraging to find that some derivatives endowed with obvious antioxidant activity, and among them the phenolic 3,4-dihydroxyl compound 6f with 7-hydroxyl in the quinoxalinone core showed the most potent activity, even comparable with the well-known antioxidant Trolox. Structure-activity relationship and docking studies highlighted the importance of phenolic hydroxyl both in C3 side chain and the core structure for constructing potent ALR2 inhibitors with antioxidant activity.     

肠呼吸抑制胁迫对大鳞副泥鳅呼吸代谢和抗氧化能力的影响

为研究肠呼吸抑制胁迫对气呼吸鱼类大鳞副泥鳅(Paramisgurnus dabryanus)的鳃和肠道呼吸代谢及抗氧化能力的影响,初步探究其生理反馈调节机制,本文选取大鳞副泥鳅成熟个体(n=60)进行肠呼吸抑制胁迫实验。分别对实验组(肠呼吸抑制,n=30)与空白对照组(n=30)的大鳞副泥鳅饲养驯化2周,测定其整体静止代谢率、呼吸频率、鳃和肠道各段的乳酸脱氢酶(LDH)、琥珀酸脱氢酶(SDH)、Na+/K+ATP酶(NKA)、过氧化氢酶(CAT)以及超氧化物歧化酶(SOD)活性。肠呼吸抑制胁迫下,实验组与对照组大鳞副泥鳅整体静止代谢率无显著差异(P0.05),而实验组大鳞副泥鳅鳃部呼吸频率显著加快(P0.05)。与对照组相比,实验组大鳞副泥鳅鳃部的琥珀酸脱氢酶活性显著升高(P0.05),而后肠琥珀酸脱氢酶和Na+/K+ATP酶显著降低(P0.05)。同时实验组大鳞副泥鳅后肠的乳酸脱氢酶活性显著升高(P0.05)。实验组和对照组之间,大鳞副泥鳅鳃和前中肠的过氧化氢酶以及超氧化物歧化酶酶活性无显著差异(P0.05),后肠则有显著性升高(P0.05)。当大鳞副泥鳅肠呼吸受到抑制时,会加强其鳃部有氧呼吸代谢,弥补肠呼吸缺失部分,满足机体生理需求,而气呼吸的后肠会有一定氧化应激反应。     

Synthesis,characterization and biological studies of Schiff bases derived from heterocyclic moiety

Some new Schiff bases (H₁-H₇) have been synthesized by the condensation of 2-aminophenol, 2-amino-4-nitrophenol, 2-amino-4-methylphenol, 2-amino benzimidazole with thiophene-2-carboxaldehyde and pyrrole-2-carboxaldehyde. The structures of newly synthesized compounds were characterized by elemental analysis, FT-IR, ¹ H NMR, UV–VIS, and single crystal X-ray crystallography. The in vitro antibacterial activity of the synthesized compounds has been tested against Salmonella typhi, Bacillus coagulans, Bacillus pumills, Escherichia coli, Bacillus circulans, Pseudomonas, Clostridium and Klebsilla pneumonia by disk diffusion method. The quantitative antimicrobial activity of the test compounds was evaluated using Resazurin based Microtiter Dilution Assay. Ampicillin was used as standard antibiotics. Schiff bases individually exhibited varying degrees of inhibitory effects on the growth of the tested bacterial species. The antioxidant activity of the synthesized compounds was determined by the 1,1-diphenyl-2-picrylhydrazyl(DPPH) method. IC₅₀ value of synthesized Schiff bases were calculated and compared with standard BHA.     

Antioxidant system is essential to increase drought tolerance of sugarcane

Drought is one of the main factors affecting the productivity of agricultural crops, and plants respond to such stress by activating various physiological and biochemical mechanisms against dehydration. The present study investigated two varieties of sugarcane (Saccharum spp.) with contrasting responses to drought (RB867515, more tolerant; and RB855536, less tolerant) and subjected them to progressive drought conditions (2, 4, 6 and 8 days) followed by rehydration. Drought caused a decrease in water potential (ψ_w) and osmotic potential (ψ_os) in the leaves, which recovered to normal levels after rehydration only up to the fourth day of drought. Water stress changed the carbon metabolism of leaves by reducing starch and sucrose contents and increasing glucose and fructose contents in both varieties. Water deficit caused a significant reduction in the maximum quantum efficiency of photosystem II (F_v/F_m) and effective quantum yield (Φ_PSII) in both varieties; however, RB867515 recovered faster after rehydration. Under water stress, the more tolerant variety RB867515 exhibited increased activity of the antioxidant enzymes catalase, ascorbate peroxidase and superoxide dismutase compared with the RB855536 variety. The results suggest that RB867515 is more tolerant to drought conditions because of a more efficient antioxidant system, which results in reduced photosynthesis photoinhibition during water stress, thus revealing itself as a potential physiological marker for drought tolerance studies.     

Changes in leaf gas exchange,chlorophyll a fluorescence and antioxidant metabolism within wheat leaves infected by Bipolaris sorokiniana

The photosynthetic performance (leaf gas exchange and chlorophyll a (Chla) fluorescence), activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX)] and the concentrations of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) in the flag leaves of plants from two wheat cultivars with contrasting levels of resistance to spot blotch was assessed. Spot blotch severity was significantly lower in plants from cv. BR‐18 compared to cv. Guamirim. Net carbon assimilation rate, stomatal conductance and concentrations of Chla, Chlab and carotenoids were significantly decreased from fungal infection. In contrast, internal CO₂ concentration was significantly increased from fungal infection in comparison to their non‐inoculated counterparts. Similarly, inoculation significantly reduced photochemical performance in the inoculated flag leaves in comparison to their non‐inoculated counterparts. However, plants from cv. BR‐18 were able to sustain greater functionality of the photosynthetic apparatus during fungal infection process compared to cv. Guamirim. The activities of SOD, POX, APX and CAT increased in inoculated flag leaves from both cultivars compared to non‐inoculated plants, and the highest increases were measured in cv. BR‐18. The greater activities of these enzymes were associated with a reduced H₂O₂ concentration in the inoculated flag leaves from cv. BR‐18, resulting, therefore, in a lower MDA concentration. Thus, a more efficient antioxidative system in flag leaves from cv. BR‐18 plays a pivotal role in removing the excess reactive oxygen species that were generated during the infection process of Bipolaris sorokiniana, therefore limiting cellular damage and largely preserving the photosynthetic efficiency of the infected flag leaves.     

小分子化合物诱导干细胞向视网膜感光细胞分化的研究进展

干细胞是一类具有多向分化潜能的细胞群,如胚胎干细胞(embryonic stem cell,ESC)、诱导多潜能干细胞(induced pluripotent stem cell,i PSC)等,可在特定的条件下向包括视网膜感光细胞在内的多种细胞分化。小分子化合物是一类由组织细胞合成、分泌的小分子多肽类因子,特定的小分子化合物可作用于干细胞诱导其向视网膜感光细胞分化。目前,对干细胞体外培养,通过使用不同的诱导培养方案,探索干细胞向视网膜感光细胞分化的研究成为热点。早期,研究者们主要在共培养条件下采用小分子化合物诱导ESC向视网膜感光细胞分化,随着研究的进展,逐渐开始探索在无共培养条件下小分子化合物诱导ESC向视网膜感光细胞的分化以及小分子化合物诱导i PSC向视网膜感光细胞的分化。本文主要就小分子化合物促进ESC和i PSC向视网膜感光细胞分化的研究进展进行综述。     

An in vitro evaluation of the effects of a Yucca schidigera extract and chestnut tannins on composition and metabolic profiles of canine and feline faecal microbiota

The in vitro effect of a Yucca schidigera extract (YSE) and tannins from chestnut wood on composition and metabolic activity of canine and feline faecal microbiota was evaluated. Four treatments were carried out: control diet, chestnut tannins (CT), YSE and CT + YSE. The YSE was added to canine and feline faecal cultures at 0.1 g/l, while CT were added at 0.3 g/l for a 24-h incubation. A total of 130 volatile compounds were detected by means of headspace-solid phase microextraction gas-chromatography/mass spectrometry analyses. Several changes in the metabolite profiles of fermentation fluids were found, including a decrease of alcohols (?19%) and esters (?42%) in feline and canine inoculum, respectively, which was due to the antibacterial properties of tannins. In canine inoculum, after 6 h, YSE + CT caused lower cadaverine concentrations (?37%), while ammonia (?4%) and quinolone (?27%) were reduced by addition of CT. After 24 h, the presence of CT resulted in a decrease of sulphur compounds, such as dimethyl sulphide (?69%) and dimethyl disulphide (?20%). In feline faecal cultures, after 6 h, CT lowered the amount of indole (?48%), whereas YSE tended to decrease trimethylamine levels (?16%). Both in canine and feline inoculum, addition of CT and, to a minor extent, YSE affected volatile fatty acids patterns. In canine faecal cultures, CT exerted a marginal inhibitory effect on Escherichia coli population (?0.45 log 10 numbers of DNA copies/ml), while enterococci were increased (+2.06 log 10 numbers of DNA copies/ml) by YSE. The results from the present study show that YSE and tannins from chestnut wood exert different effects on the composition and metabolism of canine and feline faecal microbiota. In particular, the supplementation of YSE and tannins to diets for dogs and cats may be beneficial due to the reduction of the presence of some potentially toxic volatile metabolites in the animals’ intestine.     

Essential Oil and Bioactive Compounds Variation in Myrtle (Myrtus communis L.) as Affected by Seasonal Variation and Salt Stress

The effect of different NaCl concentrations (control, 2, 4 and 6 dS/m) and three harvesting times in different seasons including spring (9 April), summer (5 July), and fall (23 September) was evaluated on essential oil (EO) yield, composition, phenolic, flavonoid content, and antioxidant activity of myrtle. Essential oil yield ranged from 0.2% in control and fall to 1.6% in moderate salinity (4 dS/m) and spring season. The main constituents obtained from gas chromatography/mass spectrometry analysis were α‐pinene, 1,8‐cineole, limonene, linalool, α‐terpineol, and linalyl acetate in which α‐pinene ranged from 11.70% in moderate and fall to 30.99% in low salinity (2 dS/m) and spring, while 1,8‐cineole varied from 7.42% in high salinity (6 dS/m) and summer to 15.45% in low salinity and spring, respectively. Salt stress also resulted in an increase in total phenolic, flavonoid content, and antioxidant activity. The highest antioxidant activity based on DPPH radical scavenging activity, reducing power (FTC) and β‐carotene/linoleic acid model systems was found in plants harvested in spring and summer in high stress condition. The lowest IC₅₀ values obtained in 6 dS/m in spring (375.23 μg/ml) followed by summer (249.41 μg/ml) and fall (618.38 μg/ml). Eight major phenolic and flavonoid compounds were determined in three harvesting times using high performance liquid chromatography analysis. In overall, late harvesting time of myrtle in fall can lead to reduce the most of major EO components, while it can improve the amount of phenolic acids.