Synthesis of aromatic-linked polyamine macrocyclic derivatives as HIV-1 entry inhibitors

A series of novel aromatic-linked polyamine macrocyclic derivatives have been synthesized. Their structures were confirmed by MS and ^1H NMR. These compounds exhibited potent anti-HIV-1 activities.

Possible Role of Cellular Polyamine Metabolism in Neuronal Apoptosis

Recent studies have shown that cellular levels of polyamines(PAs)are significantly altered in neurodegenerative diseases.Evidence from in vivo animal and in vitro cell experiments suggests that the cellular levels of various PAs may play important roles in the central nervous system through the regulation of oxidative stress,mitochondrial metabolism,cellular immunity,and ion channel functions.Dysfunction of PA metabolism related enzymes also contributes to neuronal injury and cognitive impairment in many neurodegenerative diseases.Therefore,in the current work,evidence was collected to determine the possible associations between cellular levels of PAs,and related enzymes and the development of several neurodegenerative diseases,which could provide a new idea for the treatment of neurodegenerative diseases in the future.

Effects of polyamines on the early development of cystocarps,spore release,survival,and germination rate of Gracilariopsis lemaneiformis

Three polyamines(PAs)(spermidine(Spd),spermine(Spm),and putrescine(Put))were used as growth regulators to the marine macroalgae Gracilariopsis lemaneiformis and to female gametophyte and reproductive tissues(cystocarps were constructed),which led to early maturation of cystocarps and spore release.Laboratory cultivation revealed that exogenous PA application accelerated the development of cystocarps,and the mean sporeling growth rate was 20%–50%/d during the initial week of cultivation.The spore count(SC),survival rate(SR),and germination rate(GR)of G.lemaneiformis showed different responses to PA(10-6 mol/L and 10-3 mol/L)treatments under different temperatures(18,26,and 34℃),light intensities(30,60,and 90μmol photons/(m^(2)·s)),salinities(25,30,and 35),and nutrient levels(25꞉2.5,50꞉5.0,and 75꞉7.5μmol/L NH4Cl꞉K2HPO4),and the optimal conditions were 26℃,light intensity of 60μmol/(m^(2)·s),salinity of 35,and nutrient level of 50꞉5.0μmol/L NH4Cl꞉K2HPO4.Under the optimum conditions,the SC per cystocarp increased by 82.38%,and the spore SR and GR increased by 33.07%and 46.44%,respectively.Each experiment lasted for 7 days,with the highest SC on Day 4 and plateauing on Day 7.The results indicate that PAs could promote the early maturation,spore release,survival,and germination of G.lemaneiformis under laboratory conditions.

Analysis of a Strong-Inhibition Polyamine Drilling Fluid

Drilling technologies based on oil-based drillingfluids and strong inhibitory saltwaterfluids are affected by draw-backs such as downhole accidents where sticking and wellbore instabilities occur.Existing polyamine drillingfluids also exhibit problems such as easy decomposition and poor inhibition performances.In order to mitigate these issues,additives can be used,such as polyamine inhibitors and the synthesis of nanometerfiltrate reducers.Tests conducted in the frame of this study with a polyamine drillingfluid and such additives show that thisfluid has the same inhibitory,plugging,lubricating,and wellbore-stability performances as oil-based drillingfluids.However,it has long-term anti-wear performances even better than those of oil-based drillingfluids.The out-comes of a series of comparisons with other sample cases(other wells)are reported and the advantages related to the proposedfluid discussed in detail.

两种预氧化法与氯胺消毒联用对polyamine形成NDMA的影响

预氧化处理与有机高分子絮凝剂联用会使含氮消毒副产物亚硝基二甲胺(NDMA)质量浓度上升,典型水处理工艺条件下NDMA的质量浓度为60～100 ng/L,为了解不同因素的影响及其反应机理,研究次氯酸钠氯化预氧化及高锰酸钾预氧化与聚环氧氯丙烷二甲胺(polyamine)在不同条件下联用并用氯胺消毒后NDMA的生成量.结果表明:随着预氧化剂投加量、pH、polyamine投加量及Br-质量浓度的增加,NDMA的生成量也相应增加;低质量浓度NH_4^+会导致NDMA生成量增加17. 5%左右,但随质量浓度增加,NDMA生成量逐渐减少至初始水平;随着NO_2^-质量浓度增加,NDMA生成量显著减少,当NO_2^-的质量浓度达到10 mg/L时,NDMA的生成量为最初的15%左右;氯化预氧化过程符合UDMH机理,而高锰酸钾预氧化过程包含UDMH机理及羟基自由基机理.

Relationship between ATPase activity and conjugated polyamines in mito-chondrial membrane from wheat seedling roots under osmotic stress

The effects of osmotic stress on the ATPase activity, the contents of —SH group and conjugated polyamines in mitochondrial membrane from wheat seedling [Triticum aestivum L. cv. Yumai No.18(drought-tolerant) and cv. Yumai No.9(drought-sensitive)] roots were investigated. The results showed that ATPase activity and —SH group content decreased with polyethylene glycol(PEG) 6000(-0.55 MPa) treatment for 7 d, in concert with the decrease of the ratio of noncovalently conjugated spermidine(NCC-Spd)/noncovalently conjugated putrescine(NCC-Put) and increase of the covalently conjugated putrescine(CC-Put). Osmotic stress injury to Yangmai No.9 seedlings was alleviated greatly with 1 mmol/L exogenous spermidine(Spd), in concert with marked increases of the ratio of NCC-Spd/NCC-Put, —SH group contents and ATPase activity in mitochondrial membrane. Under osmotic stress, the concomitant treatment of Yumai No.18 seedlings with methylglyoxyl bis(guanylhydrazone) (MGBG), an inhibitor of S-adenosyl methionine decarboxylase(SAMDC), and phenanthrolin (o-Phen), an inhibitor of transglutaminase(TGase), caused a significant decrease of the ratio of NCC-Spd / NCC-Put, CC-Put contents, respectively, in concert with the marked decreases of ATPase activity, —SH group content and its tolerance to osmotic stress. All the results above suggested that osmotic stress tolerance of wheat seedlings was associated with the ATPase activity, the contents of —SH group, NCC-Spd and CC-Put in mitochondrial membrane.

Effect of polyamine on seed germination of wheat under drought stress is related to changes in hormones and carbohydrates

Drought is a multifaceted stress condition that inhibits crop growth. Seed germination is one of the critical and sensitive stages of plants, and its process is inhibited or even entirely prevented by drought. Polyamines （PAs） are closely associ- ated with plant resistance to drought stress and seed germination. However, little is known about the effect of PA on the seed germination of wheat under drought stress. This study investigated the involvement of PAs in regulating wheat seed germination under drought stress. Six wheat genotypes differing in drought resistance were used, and endogenous PA levels were measured during seed germination under different water treatments. In addition, external PAwas used for seed soaking and the variation of hormones, total soluble sugar and starch were measured during the seed germination under different water treatments. These results indicated that the free spermidine （Spd） accumulation in seeds during the seed germination period favored wheat seed germination under drought stress; however, the free putrescine （Put） accumulation in seeds during the seed germination period may work against wheat seed germination under drought stress. In addition, seed soaking in Spd and spermine （Spm） significantly relieved the inhibition of seed germination by drought stress; howev- er, soaking seeds in Put had no significant effect on seed germination under drought. External Spd and Spm significantly increased the endogenous indole-3-acetic acid （IAA）, zeatin （Z）＋zeatin riboside （ZR）, abscisic acid （ABA）, and gibberellins （GA） contents in seeds and accelerated the seed starch degradation and increased the concentration of soluble sugars in seeds during seed germination. This may promote wheat seed germination under drought stress. In conclusion, free Spd and Put are key factors for regulating wheat seed germination under drought stress and the effects of Spd and Put on seed germination under drought notably related to hormones and starch metabolism.

Regulatory Function of Polyamine Oxidase-Generated Hydrogen Peroxide in Ethylene-Induced Stomatal Closure in Arabidopsis thaliana

Hydrogen peroxide （H2O2） is an important signaling molecule in ethylene-induced stomatal closure in Arabidopsis thaliana. Early studies on the sources of H2O2 mainly focused on NADPH oxidases and cell-wall peroxidases. Here, we report the involvement of polyamine oxidases （PAOs） in ethylene-induced H2O2 production in guard cells. In Arabidopsis epidermal peels, application of PAO inhibitors caused the failure of ethylene to induce H2O2 production and stomatal closure. Results of quantitative RT-PCR analysis and pharmacological experiments showed that AtPAO2 and AtPAO4 transcripts and activities of PAOs were both induced by ethylene. In transgenic Arabidopsis plants over-expressing AtPAO2 and AtPAO4, stomatal movement was more sensitive to ethylene treatment and H2O2 production was also significantly induced. The increased H2O2 production in the transgenic lines compared to the wild-type plants suggests that AtPAO2 and AtPAO4 probably are involved in ethylene-induced H2O2 production. Several factors which induce stomatal closure such as dehydration and high salinity all enhanced the expression of AtPAO2 and AtPAO4 to different degrees. Moreover, GFP- AtPAOs fusion protein localized in the nucleus, cytoplasm, and cell wall of the guard cells. Therefore, our results strongly indicated that PAO is a source of H2O2 generation in Arabidopsis guard cells and plays crucial roles in stomatal movement.

Relationship Between Polyamines Metabolism and Cell Death in Roots of Malus hupehensis Rehd. Under Cadmium Stress

The free putrescine （Put） content, the hydrogen peroxide （H202） content and the polyamine oxidase （PAO） activity in roots of Malus hupehensis Rehd. var. pinyiensis Jiang （PYTC） were significantly increased, and reached its peak at 1, 2 and 6 h, respectively, under cadmium treatment. The free spermine （Spin） and spermidine （Spd） contents were dramatically decreased, and reached the minimum value at 4-6 h, then remained relatively stable. The change in total free polyammes （PAs） content was consistent with that of free Put. The number of root dead cells was gradually increased after treatment for 24 h, and the typical characteristics of programmed cell death （PCD） were displayed at 48 h. Throughout the Cd treatment process, changes in PAs metabolism appeared to be prior to cell death increase, and the H2O2 content was always maintained at a high level. These results indicated that polyamines could initiate cell death by generating H2O2 in roots of Malus hupehensis Rehd. under CdSO4 stress.

Catalytic hydrolysis of phosphate diester (BNPP) and plasmid DNA by mononuclear macrocyclic polyamine metal complexes

The activities of the catalytic hydrolysis of phosphate diester （BNPP） [bis（p-nitrophenyl）phosphate diester] and plasmid DNA （pUC 18） by mononuclear macrocyclic polyamine metal complexes have been investigated in this paper. The results showed that the highest activity in hydrolysis of BNPP was obtained with le--Zn（II） complex （composed of lipophilic group） as catalyst. The hydrolysis rate enhancement is up to 3.64 × 10^4 fold. These metal complexes could effectively promote the cleavage of plasmid DNA （pUC18） at physiological conditions.

Melatonin treatment induces chilling tolerance by regulating the contents of polyamine,γ-aminobutyric acid,and proline in cucumber fruit

The mechanism of melatonin(MT)induced chilling tolerance in harvested cucumber fruit was investigated at commercial maturity.In this study,cucumber fruits were treated with 100μmol L^(-1) MT at 4℃ and 90% relative humidity for 15 d of storage.In comparison with the control,cucumber treatment with MT resulted in reduced chilling injury(CI),decreased electrolyte leakage and enhanced firmness.The fruits treated with MT showed higher chlorophyll contents in storage conditions with suppressed chlorophyllase enzyme activity.MT treatment increased arginine decarboxylase(ADC)and ornithine decarboxylase(ODC)enzyme activities.Moreover,enhanced expression of the Cucumis sativus ADC(CsADC)and C.sativus ODC(CsODC)genes resulted in the accumulation of polyamine contents.Similarly,proline levels exhibited higher levels among treated fruits.Meanwhile,the proline synthesizing enzymes △1-pyrroline-5-carboxylate syntheses(P5CS)and ornithine aminotransferase(OAT)were significantly increased,while a catabolic enzyme of proline dehydrogenase(PDH)activity was inhibited by treatment.In addition,MT induced expression of C.sativus OAT(CsOAT)and C.sativus P5CS(CsP5CS)genes.Cucumber fruits treated with MT also exhibited higher γ-aminobutyric acid(GABA)content by enhanced GABA transaminase(GABA-T)and glutamate decarboxylase(GAD)enzyme activities and a higher C.sativus GAD(CsGAD)gene expression.To sum up,the results show that MT treatment enhanced chilling tolerance,which was associated with the regulation of polyamines,as well as proline and γ-aminobutyric acid.

Effect of diethylstilbestrol on polyamine metabolism in hamster epididymis

<abstract>Aim: To investigate the effect of diethylstilbestrol (DES), one of the most potent endocrine disruptors, on the metabolism of polyamines in hamster epididymis. Methods: Male golden hamsters of 7-week-old were kept under a light and dark cycle of 14 h and 10 h for 1 week to stimulate maximally the gonadal function. DES was injected subcutaneously at doses of 0.01 mg·kg-1·day-1, 0.1 mg·kg-1·day-1 and 1 mg·kg-1·day-1 for one week. Results: DES treatment caused a significant decrease in the weight of epididymis. The activity of epididymal ornithine decar boxylase (ODC) increased 1 day after DES treatment, kept at a high level for 4 days and then decreased to nearly normal level at day 7. The activity of spermidine/spermine N1-acetyltransferase (SSAT) also increased transiently after DES treatment. The contents of putrescine, spermidine, spermine and N1-acetylspermidine were increased 1 day -4 days after DES treatment and restored to normal at day 7. All these changes showed a marked difference between the caput and the cauda. Conclusion: The polyamine biosynthesis in the hamster epididymis can be affected by DES, a xenoestrogen. DES may probably affect polyamine metabolism in the epididymis by regulating the rate-limiting enzymes involved in the polyamine biosynthesis.

Endogenous Levels of Polyamines under Water-Deficit Stress during Cotton’s Reproductive Development

Polyamines, putrescine (PUT), spermidine (SPD) and spermine (SPM) are implicated in plants’ responses under conditions of abiotic stress. Previous research in other crops has indicated that polyamines and changes in their concentrations are associated with drought tolerance under conditions of water-deficit stress;however, no information exists on cotton (Gossypium hirsutum L.). Growth chamber experiments were conducted with two cotton cultivars differing in drought tolerance, ST5288B2F (drought-sensitive) and Siokra L23 (drought-tolerant) in order to investigate the distribution of free polyamines, the effect of water-deficit stress on the polyamine metabolism of cotton reproductive units and their subtending leaves as well as the possible relationship between polyamines and drought tolerance in cotton. Our results showed that cotton ovaries contained significantly higher levels of total free polyamines compared to their subtending leaves under both control and water stress conditions. Water-deficit stress significantly increased PUT concentrations in ST5288B2F, while SPM levels significantly decreased in Siokra L23. The results indicated that water-deficit stress significantly affected cotton polyamine metabolism in reproductive structures and their subtending leaves;however, no clear relationship between drought-tolerance and changes in polyamine accumulation was established. Further research is needed to elucidate the mechanism according to which water-deficit stress affects polyamine metabolism.

Polyamines mediate the effect of post-anthesis soil drying on starch granule size distribution in wheat kernels

Polyamines(PAs) are important endogenous plant growth regulators responding to environmental stress and mediating many physiological processes including grain filling in cereals.This study investigated whether PAs mediate the effect of post-anthesis soil drying on starch granule size distribution,starch content,and weight of superior and inferior kernels of wheat(Triticum aestivum L.).Two wheat cultivars were grown in pots.Three treatments,well-watered(WW),moderate soil drying(MD) and severe soil drying(SD),were imposed from 9 days post-anthesis until maturity.PA levels in kernels and small,medium and large granules were measured.The results showed that superior kernels had much higher free spermidine(Spd) and free spermine(Spm) concentrations,larger volumes of medium starch granules,and smaller-sized large granules than did inferior kernels under all the treatments.Compared to WW,MD significantly increased the concentrations of free Spd and free Spm,activities of soluble starch synthase and granule-bound starch synthase,volume of medium granules,and starch content and kernel weight of inferior kernels,and decreased the size of large granules.SD produced the opposite effect.Application of Spd or Spm to spikes produced effects similar to those of MD,and application of an inhibitor of Spd and Spm synthesis produced effects similar to those of SD.These results suggest that PAs mediate the effect of post-anthesis soil drying on starch biosynthesis in wheat kernels by regulating key enzymes in starch synthesis and that elevated PA levels under MD increase the volume of medium granules and kernel weight of inferior kernels.

Protective Effect of Hydrogen Peroxide against Paraquat Toxicity in Young Pea Plants: Possible Role of Endogenous Polyamines

Young pea plants grown as a water culture were sprayed with hydrogen peroxide and 24 h later were treated with the herbicide paraquat. The effects of paraquat and H2O2 treatment were investigated on the endogenous concentrations of free proline, and free and conjugated putrescine, spermidine and spermine. Application of PQ increased the free proline and Put, and decreased conjugated and bound polyamines. The results clearly demonstrate the oxidative damages provoked by PQ application. Single treatment with H2O2 provoked considerable decrease in the free fraction of the three PAs studied 2 h after light exposition, but caused an increase in their respective conjugated fractions. Data suggest that PA changes after H2O2 treatment are due to conversion from free to conjugated form. Three hours later free PAs in H2O2 treated-plants reached control levels;however the conjugated remained higher than the control. No alterations were detected in proline concentration after H2O2 treatment. Pretreatment with Н2О2 activated some component of the plant protection mechanisms by causing an alteration in free/conjugated PAs ratio in plants subsequently subjected to PQ treatment. Data concerning PA and proline concentrations in plants treated with both compounds supposed that H2O2 shows a protective role against PQ and improves the plant tolerance to the oxidative stress generated by paraquat.

Assessment of Polyamines and Trehalose in Wheat Microspores Culture for Embryogenesis and Green Regenerated Plants

Most aspects of microspore culture protocol have the capacity to cause stress to microspores, hence, less stressful treatments might be required to avoid deleterious effects. In stressed plants, polyamines and trehalose can act as compatible solutes or osmoprotectants by stabilizing proteins and biological membranes. To improve green plant regeneration in wheat microspore culture, this study assessed the effects of polyamines (putrecine, spermidine, spermine) and trehalose on androgenic response namely embryogenesis, green plant regeneration and ploidy of green plants regenerated in three spring wheat genotypes. Microspores of the genotypes produced significant numbers of embryos and green plants among polyamine treatments but trehalose had no effect (P ≤ 0.05). Polyamine treatments for 30 min generally produced more green plants per 100 microspores than the 60 min treatments in all three genotypes. At least three out of twelve polyamine treatments in each genotype improved the production of double haploid plants and seed setting in regenerants. Wheat genotype, concentration and duration of polyamine treatment had significant impact on embryogenesis and regeneration of green plants in this study. The study also showed that polyamines could be used to accelerate cultivar development in wheat breeding.

Study on changes of polyamine levels in mice with the development of U14 cervical cancer

This study was performed to investigate the possible involvement of polyamincs in the development of cervical cancer. The objective of the present study was therefore to lind the specilic polyamine indicators, which could be used as useful markers for the early determination of cervical cancer. A simple method for the simultaneous determination of plasma concentrations ol live polyamines in normal and UI4 model mice was developed by using HPLC-MS. The samples were derivatized by benzoyl chloride. The derived polyamines were separated on a C18 colunm by a gradient elution with methanol water, and then detected with HPLC-MS. The results showed tha! all polyamine levels in the U 14 model mice were higher than those in normal ones. Thc cadaverine. putrescine and 1,3-diaminopropane levels were significantly higher in U 14 model mice plasma than those in normal mice plasma, especially the putrescine and 1, 3-diaminopropane （P〈0.01）. The cadaverine, putrescine and 1, 3-diaminopropane levels were significantly higher in U 14 mice model urine than those in normal mice urine, especially the cadaverine and 1, 3-diaminopropane （P〈0.01）. Putrescine, cadaverine and I, 3-diaminopropane might be the indicators of the cervical cancer.

The synthesis and molecular recognization of the polyamine transporter of hydrazine-modified diamine conjugates

A series of four novel hydrazine-modified diamine conjugates （7a-b, 8a-b） were synthesized and evaluated for cytotoxicity against Melanoma B 16, α-difluoromethylornithine （DFMO）-treated B 16, spermidine （SPD）-treated B 16, Mouse leukemia L 1210 and Hela cell lines. Both the DFMO-B 16 and SPD-B 16 experiments indicated that conjugates 7a-b and 8a-b could recognize the polyamine transporter （PAT） and enter the cells in part or in whole via PAT, although they were not as efficient as the reference, 9- anthracenemethyl homospermidine （1）. 2007 Chao Jie Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

CLONING AND EXPRESSION OF A GENE ASS0CIATE WITH HL_(60)CELL APOPTOSIS INDUCED BY INHIBITIONOF POLYAMINE BIOSYNTHESIS

Objective: To clone the gene associated with apoptosis induced by an inhibitor of polyamine biosynthesis, a-difluoromethylornithime(DFMO). Methods: The differential sufbtraction sereening was used for gene cloning from cDNA library of HL60 cells treated by DFMO. Northern blot,morphological observation, FCM assays and ladder map of DNA electrophoresis were performed. Results: The transfectiong gene expression and activity of inducing apoptosis in the cell transfected from recombinant plasmid containing the cloned fragment df4 wasproved. Conclusion: It is suggest that df4 gene cloned in the study coul be a gene regulating apoptosis of HL60 cells.

The effect of leaf presence on the rooting of stem cutting of bitter melon and on changes in polyamine levels

The study was conducted to investigate the optimal hormone treatment for rooting in bitter melon and the effect of defoliation on rooting and polyamine levels. Commercial preparation (diluted 1:10 and 1:20) gave extensive rooting within five days after treatment. The presence of leaf with the stem cutting was necessary for optimal rooting as defoliation drastically reduced rooting even when the rooting time was extended from 5 to 10 days. The presence of leaf also promoted the levels of putrescine three days after the hormone treatment just at the time of root emergence. Cuttings that did not have leaf did not show an increase in putrescine levels and did not produce roots. Spermidine levels also increased in the cuttings that rooted but there was no change in the levels of spermine in the cuttings that rooted. It appears that putrescine and spermidine play a role in regulating rooting in bitter melon cuttings. The vegetative propagation conditions described show that it is a practically viable technique for small growers to produce large number of plantlets at the farm for selection and cultivation.