Protein disulfide isomerase-P5, down-regulated in the final stage of boar epididymal sperm maturation,catalyzes disulfide formation to inhibit protein function in oxidative refolding of reduced denatured lysozyme

In mammalian spermiogenesis, sperm mature during epididymal transit to get fertility. The pig sharing many physiological similarities with humans is considered a promising animal model in medicine. We examined the expression profiles of proteins from boar epididymal caput, corpus, and cauda sperm by two-dimensional gel electrophoresis and peptide mass fingerprinting. Our results indicated that protein disulfide isomerase-P5 (PDI-P5) human homolog was down-regulated from the epididymal corpus to cauda sperm, in contrast to the constant expression of protein disulfide isomerase A3 (PDIA3) human homolog. To examine the functions of PDIA3 and PDI-P5, we cloned and sequenced cDNAs of pig PDIA3 and PDI-P5 protein precursors. Each recombinant pig mature PDIA3 and PDI-P5 expressed in Escherichia coli showed thiol-dependent disulfide reductase activities in insulin turbidity assay. Although PDIA3 showed chaperone activity to promote oxidative refolding of reduced denatured lysozyme, PDI-P5 exhibited anti-chaperone activity to inhibit oxidative refolding of lysozyme at an equimolar ratio. SDS-PAGE and Western blotting analysis suggested that disulfide cross-linked and non-productively folded lysozyme was responsible for the anti-chaperone activity of PDI-P5. These results provide a molecular basis and insights into the physiological roles of PDIA3 and PDI-P5 in sperm maturation and fertilization.     

Degradation of 2,4,6-tribromophenol and 2,4,6-trichlorophenol by aerobic heterotrophic bacteria present in psychrophilic lakes

Halogenated compounds have been incorporated into the environment, principally through industrial activities. Nonetheless, microorganisms able to degrade halophenols have been isolated from neither industrial nor urban environments. In this work, the ability of bacterial communities from oligotrophic psychrophilic lakes to degrade 2,4,6-tribromophenol and 2,4,6-trichlorophenol, and the presence of the genes tcpA and tcpC described for 2,4,6-trichlorophenol degradation were investigated. After 10 days at 4°C, the microcosms showed the ability to degrade both halophenols. Nonetheless, bacterial strains isolated from the microcosms did not degrade any of the halophenols, suggesting that the degradation was done by a bacterial consortium. Genes tcpA and tcpC were not detected. Results demonstrated that the bacterial communities present in oligotrophic psycrophilic lakes have the ability to degrade halophenolic compounds at 4°C and the enzymes involved in their degradation could be codified in genes different to those described for bacteria isolated from environments contaminated by industrial activities.     

Synthesis and antimicrobial activity of brominated resorcinol dimers

Dibrominated resorcinol dimers were synthesized by reaction of 4-bromoresorcinol with aldehydes under reflux in ethanol in the presence of HCl. Subsequent dehalogenation yielded the corresponding monobrominated compounds and a fully dehalogenated dimer. Of the dimers, 6,6'-((4-hydroxyphenyl)methylene)bis(4-bromobenzene-1,3-diol) (4) displayed potent antibacterial activity and inhibitory activity against isocitrate lyase Candida albicans.     

The first synthesis,carbonic anhydrase inhibition and anticholinergic activities of some bromophenol derivatives with S including natural products

Starting from vanillin, known four benzyl bromides with Br were synthesized. The first synthesis of natural product 3,4-dibromo-5-((methylsulfonyl)methyl)benzene-1,2-diol (2) and 3,4,6-tribromo-5-((methylsulfonyl)methyl)benzene-1,2-diol (3) and derivatives were carried out by demethylation, acetylatilation, oxidation and hydrolysis reactions of the benzyl bromides. Also, these compounds were tested against some important enzymes like acetylcholinesterase and butyrylcholinesterase enzymes, carbonic anhydrase I, and II isoenzymes. The novel bromophenols showed Ki values of in range of 53.75 ± 12.54–234.68 ± 46.76 nM against hCA I, 42.84 ± 9.36 and 200.54 ± 57.25 nM against hCA II, 0.84 ± 0.12–14.63 ± 3.06 nM against AChE and 0.93 ± 0.20–18.53 ± 5.06 nM against BChE. Induced fit docking process performed on the compounds inhibiting hCA I, hCA II, AChE, and BChE receptors. Hydroxyl group should exist at the aromatic ring of the compounds for inhibition of the enzymes. The moieties reported in this study will be useful for design of more potent and selective inhibitors against the enzymes.     

Enhanced dye decolorization efficiency by citraconic anhydride-modified horseradish peroxidase

Bromophenol blue and methyl orange removal capabilities of citraconic anhydride-modified horseradish peroxidase were compared with those of native horseradish peroxidase. Citraconic anhydride-modified horseradish peroxidase showed higher decolorization efficiencies for both dyes than native horseradish peroxidase. Upon the chemical modification, the decolorization efficiencies were increased by 1.8% and 12.4% for bromophenol blue and methyl orange, respectively. The quantitative relationships between decolorization efficiencies of dyes and reaction conditions were also investigated. Experimental data revealed that aqueous phase pH, reaction time, temperature, enzyme concentration and ratio of dye and H₂O₂ play a significant role on the dye degradation. Lower dose of citraconic anhydride-modified horseradish peroxidase was required than that of native enzyme for the decolorizations of both dyes to obtain the same decolorization efficiencies. Citraconic anhydride-modified HRP exhibited a good decolorization of dye over a wide range of dye concentration from 8 to 24 or 32 μmol l⁻¹ at 300 μmol l⁻¹ H₂O₂, which would match industrial expectations. Kinetic constants for two different dyes were also determined. Citraconic anhydride-modified horseradish peroxidase shows greater affinity and catalytic efficiency than native horseradish peroxidase for both dyes.     

Synthesis and biological evaluation of bromophenol derivatives with cyclopropyl moiety: Ring opening of cyclopropane with monoester

Trans-(1R*,2R*,3R*)-Ethyl 2-(3,4-dimethoxyphenyl)-3-methylcyclopropane-1-carboxylate (6) and its cis isomer 7 were obtained from the reaction of the methyl isoeugenol (5) with ethyl diazoacetate. The reduction and bromination reactions of the ester 6 and 7 together with the hydrolysis of all esters were carried out. Opening ring of cyclopropane was observed in the reaction of 7 with bromine. The opening of cyclopropane ring with COOR and synthesis of esters, alcohols and acids (6–26) are new. These obtained bromophenol derivatives (6–26) were effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms (hCA I and II) and acetylcholinesterase (AChE) enzymes with Ki values in the range of 7.8 ± 0.9–58.3 ± 10.3 nM for hCA I, 43.1 ± 16.7–150.2 ± 24.1 nM for hCA II, and 159.6 ± 21.9–924.2 ± 104.8 nM for AChE, respectively. Acetylcholinesterase inhibitors are the most popular drugs applied in the treatment of diseases such as Alzheimer’s disease, Parkinson’s disease, senile dementia, and ataxia, among others.     

海藻溴酚化合物对糖尿病大鼠抗氧化水平的影响

目的:本研究通过建立糖尿病大鼠动物模型,观察海藻溴酚化合物A、B对糖尿病大鼠机体抗氧化水平的影响。方法:采用STZ注射法制作糖尿病(DM)大鼠模型,随机分为空白对照组、糖尿病模型组、化合物A低剂量组及高剂量组、化合物B低剂量组及高剂量组,灌胃给药12周。12周末处死大鼠,测肾匀浆中谷胱甘肽过氧物酶(GSH-Px)的活力及丙二醛(MDA)的含量;并采用透射电镜观察大鼠肾组织的病理改变。结果:与空白对照组相比,糖尿病模型组肾组织匀浆中GSH-Px活力下降,MDA含量升高,差异有统计学意义(P<0.05)。各干预组中GSH-Px的活力较糖尿病模型组有升高的趋势,MDA含量有下降趋势。电镜下各干预组肾小球及肾小管病变较糖尿病组减轻,且高剂量组优于低剂量组。结论:溴酚化合物A、B能提高糖尿病大鼠机体抗氧化水平,并能一定程度的改善肾脏病理改化,但其具体机制有待进一步探讨。     

Potent alpha-glucosidase inhibitors purified from the red alga Grateloupia elliptica

Diabetes mellitus is a most serious and chronic disease whose incidence rates are increasing with incidences of obesity and aging of the general population over the world. One therapeutic approach for decreasing postprandial hyperglycemia is to retard absorption of glucose by inhibition of α-glucosidase. Two bromophenols, 2,4,6-tribromophenol and 2,4-dibromophenol, were purified from the red alga Grateloupia elliptica. IC₅₀ values of 2,4,6-tribromophenol and 2,4-dibromophenol were 60.3 and 110.4 μM against Saccharomyces cerevisiae α-glucosidase, and 130.3 and 230.3 μM against Bacillus stearothermophilus α-glucosidase, respectively. In addition, both mildly inhibited rat-intestinal sucrase (IC₅₀ of 4.2 and 3.6 mM) and rat-intestinal maltase (IC₅₀ of 5.0 and 4.8 mM). Therefore, bromophenols of G. elliptica have potential as natural nutraceuticals to prevent diabetes mellitus because of their high α-glucosidase inhibitory activity.     

Antibacterial bromophenols from the marine red alga Rhodomela confervoides

Two bromophenols, together with three known compounds, were isolated from the methanolic extract of the marine alga, Rhodomela confervoides. By means of MS and NMR spectroscopic analyses, they were identified as 3-bromo-4-[2,3-dibromo-4,5-dihydroxyphenyl] methyl-5-(hydroxymethyl) 1,2-benzenediol (1) and 3-bromo-4-[2,3-dibromo-4,5-dihydroxyphenyl] methyl-5- (ethoxymethyl) 1,2-benzenediol (2). Three known compounds were also isolated, namely 3-bromo-4-[2,3-dibromo-4,5-dihydroxyphenyl] methyl-5-(methoxymethyl) 1,2-benzenediol (3), 4,4'- methylenebis [5,6-dibromo-1,2-benzenediol] (4) and bis (2,3-dibromo-4,5-dihydroxybenzyl) ether (5). Compound 5 was the most active against five strains of bacteria with the MIC less than 70 microg/ml, while compounds 2, 3 and 4 exhibited moderate activity.