Tyrosyl-tRNA synthetase inhibitors as antibacterial agents: synthesis, molecular docking and structure-activity relationship analysis of 3-aryl-4-arylaminofuran-2(5H)-ones.

Thirty-five 3-aryl-4-arylaminofuran-2(5H)-one derivatives were designed, prepared and tested for their inhibitory activity against tyrosyl-tRNA synthetase. Out of these compounds, 3-(3-bromophenyl)-4-(3,5-dichlorophenylamino)furan-2(5H)-one (35) was the most active with IC(50) of 0.09 ± 0.02 µM. The structure-activity relationship revealed that introduction of chlorine atoms at both meta positions of aniline moiety significantly increased the enzyme inhibitory activity. The results of antibacterial assay revealed that the tested compounds showed good activity against Gram-positive bacteria, with 35 being the most potent with MIC(50) of 0.06 µg/mL against Staphylococcus aureus ATCC 25923. Molecular docking of 35 into S. aureus tyrosyl-tRNA synthetase active site was also performed. The inhibitor snugly fitting the active site may well explain its excellent inhibitory activity.

The synthesis, structure and activity evaluation of pyrogallol and catechol derivatives as Helicobacter pylori urease inhibitors.

Some pyrogallol and catechol derivatives were synthesized, and their urease inhibitory activity was evaluated by using acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor, as positive control. The assay results indicate that many compounds have showed potential inhibitory activity against H. pylori urease. 4-(4-Hydroxyphenethyl)phen-1,2-diol (2a) was found to be the most potent urease inhibitor with IC(50)s of 1.5±0.2 µM for extracted fraction and 4.2±0.3 µM for intact cell, at least 10 times and 20 times lower than those of AHA (IC(50) of 17.2±0.9 µM, 100.6±13 µM), respectively. This finding indicate that 2a would be a potential urease inhibitor deserves further research. Molecular dockings of 2a into H. pylori urease active site were performed for understanding the good activity observed.

[Bioaccumulation of sediment heavy metals in Bellamya aeruginosa and its relations with the metals geochemical fractions].

A 28-day sediment bioaccumulation test was conducted to study the bioaccumulation of river sediment heavy metals in Bellamya aeruginosa, and its relations with the geochemical fractions of the metals. A higher bioaccumulation of Cd, Pb, Cu, Cr, Zn, and Mn was found in the hepatopancreas of B. aeruginosa, with the greatest accumulation of Zn (84.32% +/- 4.36%), followed by Cu (7.67% +/- 2.84%), Pb (3.62% +/- 1.84%), Cr (2.22% +/- 1.03%), Mn (1.33% +/- 0.15%), and Cd (0.83% +/- 0.53%). No significant correlations were observed between the heavy metals accumulations in B. aeruginosa hepatopancreas, but the significant positive correlation between the metals pollution index of hepatopancreas and the Nemerow pollution index of sediments suggested that B. aeruginosa could be used as a potential bioindicator for sediment heavy metals pollution. The biota-sediment accumulation factors (BSAFs) for Cd, Cr, Zn, and Mn from different sediments showed a higher variability, while the BSAFs for Cu and Pb were relatively constant. The bioaccumulation of Cd had significant correlations with exchangeable Cd, weak acid soluble Cd, and oxidizable Cd; Pb bioaccumulation had significant correlation with reducible Pb; Cu bioaccumulation had significant correlation with oxidizable Cu; while Cr and Mn bioaccumulation had no correlations with the total concentrations and geochemical fractions of the two metals. Therefore, it would be inappropriate to use the BSAF as the indicator for the bioaccumulation of heavy metals in B. aeruginosa.

[Leaf cell damage and changes in photosynthetic pigment contents of three moss species under cadmium stress].

A hydroponic experiment was conducted to study the leaf cell damage and the changes in photosynthetic pigment contents of three moss species under Cd stress, aimed to reveal the Cd sensibility and tolerance of the species. Even though the Cd stress was relatively low (1 mg Cd x L(-1)), the leaf cells of Dolichomitriopsis diversiformis and Plagiomnium acutum were damaged. With the increasing level of Cd stress, the leaf cell damage of the three moss species aggravated significantly, and the resulted damage under high level (100 mg x L(-1)) Cd stress was in the order Brachythecium procumbens > P. acutum > D. diversiformis. Relatively low (1 mg x L(-1)) Cd stress had no significant effects on the total chlorophyll content of the three species. However, with the increase of Cd stress (> or = 10 mg x L(-1)), the total chlorophyll content decreased significantly, with the order of B. procumbens > P. acutum > D. diversiformis. The Cd stress at 1 and 10 mg x L(-1) had no significant effects on the chlorophyll a/b, but the Cd stress at 100 mg x L(-1) led to a significant decrease of chlorophyll a/b in P. acutum and B. procumbens. The maximal decline of carotenoid content in B. procumbens was observed at 1 mg x L(-1) of Cd. The three moss species could significantly enrich Cd, and the Cd enrichment was D. diversiformis > P. acutum > B. procumbens. The leaf cell damage rate and the changes of chlorophyll and carotenoid contents could be used to indicate the differences in the sensitivity of D. diversiformis, P. acutum, and B. procumbens to Cd stress. D. diversiformis had the strongest tolerance to Cd stress, while P. acutum and B. procumbens had weaker tolerance. The tolerance of the three moss species to Cd stress was positively correlated to the capability of their Cd enrichment.

Endocrine disrupting effects on Chinese rare minnow (Gobiocypris rarus) fed with field collected Limnodrilus sp.

The potential endocrine disrupting effects and other toxicity effects on aquatic biota resulted from food uptake was simulated by feeding the laboratory cultured rare minnow( Gobiocypris rarus) with field collected Limnodrilus sp. The results indicated that the food chain processes affected significantly the growth, slightly reduced gonadosomatic indices, and elevated hepatosomatic indices. There was an obvious vitellogenin(VTG) induction, which generally only occurred in mature female, in the serum of juvenile rare minnow and mature male when fed with Limnodrilus sp. In addition, the rare minnow feeding on Limnodrilus sp. had significantly high renal indices, it meant obvious renal hyperplasia. The present work suggested that Limnodrilus sp. from field water may contain toxic pollutants and could lead to endocrine disruption effects to the predators. It was concluded that endocrine disruptors may not only be assimilated through water, but also be bioconcentrated through food web. The results also suggested the importance of food selection in conducting the study of endocrine disruption effects using sensitive species.