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ChemistryOpen Oct 2022Antibiotic resistance is now a growing threat to human health, further exacerbated by the lack of new antibiotics. We describe the practical synthesis of a series of...
Antibiotic resistance is now a growing threat to human health, further exacerbated by the lack of new antibiotics. We describe the practical synthesis of a series of substituted polyamine succinamides and branched polyamines that are potential new antibiotics against both Gram-positive and Gram-negative bacteria, including MRSA and Pseudomonas aeruginosa. They are prepared via 1,4-Michael addition of acrylonitrile and then hydrogenation of the nitrile functional groups to primary amines. They are built upon the framework of the naturally occurring polyamines thermine (3.3.3, norspermine) and spermine (3.4.3), homo- and heterodimeric polyamine succinic amides. Linking two of the same or different polyamines together via amide bonds can be achieved by introducing a carboxylic acid group on the first polyamine, then coupling that released carboxylic acid to a free primary amine in the second polyamine. If the addition of positive charges on the amino groups along the polyamine chains are a key factor in their antimicrobial activity against Gram-negative bacteria, then increasing them will increase the antimicrobial activity. Synthesising polyamine amide dimers will increase the total net positive charge compared to their monomers. The design and practical synthesis of such homo- and hetero-dimers of linear polyamines, spermine and norspermine, are reported. Several of these compounds do not display significant antibacterial activity against Gram-positive or Gram-negative bacteria, including MRSA and Pseudomonas aeruginosa. However, the most charged analogue, a branched polyamine carrying eight positive charges at physiological pH, displays antibiofilm activity with a 50 % reduction in PAO1 at 16-32 μg mL .
Topics: Humans; Polyamines; Spermine; Gram-Negative Bacteria; Anti-Bacterial Agents; Gram-Positive Bacteria; Acrylonitrile; Amides; Carboxylic Acids
PubMed: 36284254
DOI: 10.1002/open.202200147 -
Nutrients Nov 2020Polyamines (including putrescine, spermidine, and spermine) are small, cationic molecules that are necessary for cell proliferation and differentiation. Few studies have...
Polyamines (including putrescine, spermidine, and spermine) are small, cationic molecules that are necessary for cell proliferation and differentiation. Few studies have examined the association of dietary polyamines intake with colorectal cancer risk. The aim of this study was to evaluate total polyamines, putrescine, spermidine, and spermine intake in relation to colorectal cancer risk in China. In total, 2502 colorectal cancer cases and 2538 age-(5-year interval) and sex-matched controls were recruited from July 2010 to April 2019. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by multivariable unconditional logistic regression after adjustment for various potential confounding factors. Higher intake of total polyamine, putrescine and spermidine was significantly associated with reduced risk of colorectal cancer. The adjusted ORs for the highest compared with the lowest quartile of intake were 0.60 (95% CI 0.50, 0.72; < 0.001) for total polyamines, 0.35 (95% CI 0.29, 0.43; < 0.001) for putrescine and 0.79 (95% CI 0.66, 0.95; = 0.001) for spermidine, respectively. However, higher intake of spermine was associated with increased risk of colorectal cancer, with an adjusted OR of 1.58 (95% CI 1.29, 1.93; < 0.001). This data indicate that higher intake of total polyamines, putrescine and spermidine, as well as lower intake of spermine, is associated with a decreased risk of colorectal cancer.
Topics: Adult; Aged; Case-Control Studies; China; Colonic Neoplasms; Diet; Female; Humans; Male; Middle Aged; Odds Ratio; Polyamines; Putrescine; Rectal Neoplasms; Risk Factors; Spermidine; Spermine
PubMed: 33266410
DOI: 10.3390/nu12113575 -
Genes Apr 2022Cotton is an important agro-industrial crop providing raw material for the textile industry. Fiber length is the key factor that directly affects fiber quality. ADC,...
Cotton is an important agro-industrial crop providing raw material for the textile industry. Fiber length is the key factor that directly affects fiber quality. ADC, arginine decarboxylase, is the key rate-limiting enzyme in the polyamine synthesis pathway; whereas, there is no experimental evidence that ADC is involved in fiber development in cotton yet. Our transcriptome analysis of the fiber initiation material of L. showed that the expression profile of was induced significantly. Here, , the allele of in tetraploid upland cotton L., exhibited up-regulated expression pattern during fiber elongation in cotton. Levels of polyamine are correlated with fiber elongation; especially, the amount of putrescine regulated by ADC was increased. Scanning electron microscopy showed that the fiber length was increased with exogenous addition of an ADC substrate or product putrescine; whereas, the fiber density was decreased with exogenous addition of an ADC specific inhibitor. Next, genome-wide transcriptome profiling of fiber elongation with exogenous putrescine addition was performed to determine the molecular basis in . A total of 3163 differentially expressed genes were detected, which mainly participated in phenylpropanoid biosynthesis, fatty acid elongation, and sesquiterpenoid and triterpenoid biosynthesis pathways. Genes encoding transcription factors , , and were enriched. Therefore, these results suggested the and putrescine involvement in the development and fiber elongation of , and provides a basis for cotton fiber development research in future.
Topics: Carboxy-Lyases; Cotton Fiber; Gossypium; Putrescine
PubMed: 35627169
DOI: 10.3390/genes13050784 -
International Journal of Molecular... Nov 2022Polyamines (PA) play an important role in the growth, development and stress resistance of plants, and arginine decarboxylase (ADC) is one of the key enzymes in the...
Polyamines (PA) play an important role in the growth, development and stress resistance of plants, and arginine decarboxylase (ADC) is one of the key enzymes in the biosynthetic pathway of polyamines. Previously, the transcriptional regulation of the 'Manaohong' cherry under the shelter covering was carried out, and the PA synthase-related genes, particularly the ADC gene, were differentially expressed as exposure to drought stress. However, the mechanisms of how ADC is involved in the response of cherry to abiotic stress (especially drought stress) are still unknown. In the present work, the full-length coding sequence of this gene was isolated and named . Bioinformatics analysis indicated that the coding sequence of was 2529 bp in length. Cluster analysis showed that had the highest homologies with those of sweet cherry (, XP_021806331) and peach (, XP_007200307). Subcellular localization detected that the was localized in the plant nucleus. The qPCR quantification showed that was differentially expressed in roots, stems, leaves, flower buds, flowers, and fruits at different periods. Drought stress treatments were applied to both wild-type (WT) and transgenic s lines, and relevant physiological indicators were measured, and the results showed that the putrescine content of transgenic was higher than that of WT under high-temperature treatment. The results showed that the MDA content of WT was consistently higher than that of transgenic plants and that the degree of stress in WT was more severe than in transgenic , indicating that transgenic was able to enhance the stress resistance of the plants. Both the transgenic and WT plants had significantly higher levels of proline in their leaves after the stress treatment than before, but the WT plant had lower levels of proline than that of transgenic s in both cases. This shows that the accumulation of proline in the transgenic plants was higher than that in the wild type under drought and high and low-temperature stress, suggesting that the transgenic plants are more stress tolerant than the WT. Taken together, our results reveal that, under drought stress, the increase in both expressions of gene and Put (putrescine) accumulation regulates the activity of ADC, the content of MDA and Pro to enhance the drought resistance of
Topics: Arabidopsis; Droughts; Gene Expression Regulation, Plant; Plant Proteins; Plants, Genetically Modified; Polyamines; Proline; Prunus; Putrescine; Stress, Physiological
PubMed: 36499268
DOI: 10.3390/ijms232314943 -
Scientific Reports Mar 2018This work reports a Lactobacillus rossiae strain (L. rossiae D87) isolated from sourdough that synthesizes putrescine - a biogenic amine that raises food safety and...
This work reports a Lactobacillus rossiae strain (L. rossiae D87) isolated from sourdough that synthesizes putrescine - a biogenic amine that raises food safety and spoilage concerns - from arginine via the ornithine decarboxylase (ODC) pathway. The odc and potE genes were identified and sequenced. These genes respectively encode ornithine decarboxylase (Odc), which participates in the decarboxylation of ornithine to putrescine, and the ornithine/putrescine exchanger (PotE), which exchanges ornithine for putrescine. Transcriptional analysis showed that odc and potE form an operon that is regulated transcriptionally by ornithine in a dose-dependent manner. To explore the possible role of the ODC pathway as an acid stress resistance mechanism for this bacterium, the effect of acidic pHs on its transcriptional regulation and on putrescine biosynthesis was analysed. Acidic pHs induced the transcription of the odc-potE genes and the production of putrescine over that seen at neutral pH. Further, putrescine production via the ODC system improved the survival of L. rossiae D87 by counteracting the acidification of the cytoplasm when the cells were subjected to acidic conditions. These results suggest the ODC pathway of L. rossiae D87 provides a biochemical defence mechanism against acidic environments.
Topics: Arginine; Bacterial Proteins; Bread; Gene Expression Regulation, Bacterial; Hydrogen-Ion Concentration; Lactobacillus; Multigene Family; Operon; Ornithine; Ornithine Decarboxylase; Phylogeny; Putrescine
PubMed: 29507315
DOI: 10.1038/s41598-018-22309-6 -
Scientific Reports May 2023Aging is closely associated with the increased morbidity and mortality of ischemic cardiovascular disease, at least partially through impaired angiogenic capacity....
Aging is closely associated with the increased morbidity and mortality of ischemic cardiovascular disease, at least partially through impaired angiogenic capacity. Endothelial cells (ECs) play a crucial role in angiogenesis, and their angiogenic capacity declines during aging. Spermidine is a naturally occurring polyamine, and its dietary supplementation has exhibited distinct anti-aging and healthy lifespan-extending effects in various species such as yeast, worms, flies, and mice. Here, we explore the effects of spermidine supplementation on the age-related decline in angiogenesis both in vitro and in vivo. Intracellular polyamine contents were reduced in replicative senescent ECs, which were subsequently recovered by spermidine supplementation. Our findings reveal that spermidine supplementation improved the declined angiogenic capacity of senescent ECs, including migration and tube-formation, without affecting the senescence phenotypes. Mechanistically, spermidine enhanced both autophagy and mitophagy, and improved mitochondrial quality in senescent ECs. Ischemia-induced neovascularization was assessed using the hind-limb ischemia model in mice. Limb blood flow recovery and neovascularization in the ischemic muscle were considerably impaired in aged mice compared to young ones. Of note, dietary spermidine significantly enhanced ischemia-induced angiogenesis, and improved the blood flow recovery in the ischemic limb, especially in aged mice. Our results reveal novel proangiogenic functions of spermidine, suggesting its therapeutic potential against ischemic disease.
Topics: Animals; Mice; Spermidine; Endothelial Cells; Cardiovascular Physiological Phenomena; Ischemia; Polyamines; Neovascularization, Pathologic
PubMed: 37221395
DOI: 10.1038/s41598-023-35447-3 -
Biomolecules Mar 2022Polyamines (PAs) are small, versatile molecules with two or more nitrogen-containing positively charged groups and provide widespread biological functions. Most of these... (Review)
Review
Polyamines (PAs) are small, versatile molecules with two or more nitrogen-containing positively charged groups and provide widespread biological functions. Most of these aspects are well known and covered by quite a number of excellent surveys. Here, the present review includes novel aspects and questions: (1) It summarizes the role of most natural and some important synthetic PAs. (2) It depicts PA uptake from nutrition and bacterial production in the intestinal system following loss of PAs via defecation. (3) It highlights the discrepancy between the high concentrations of PAs in the gut lumen and their low concentration in the blood plasma and cerebrospinal fluid, while concentrations in cellular cytoplasm are much higher. (4) The present review provides a novel and complete scheme for the biosynthesis of Pas, including glycine, glutamate, proline and others as PA precursors, and provides a hypothesis that the agmatine pathway may rescue putrescine production when ODC knockout seems to be lethal (solving the apparent contradiction in the literature). (5) It summarizes novel data on PA transport in brain glial cells explaining why these cells but not neurons preferentially accumulate PAs. (6) Finally, it provides a novel and complete scheme for PA interconversion, including hypusine, putreanine, and GABA (unique gliotransmitter) as end-products. Altogether, this review can serve as an updated contribution to understanding the PA mystery.
Topics: Central Nervous System; Neuroglia; Polyamines; Putrescine; Spermine
PubMed: 35454090
DOI: 10.3390/biom12040501 -
Biomolecules May 2023The biogenic polyamines, spermidine (Spd) and spermine (Spm), are present at millimolar concentrations in all eukaryotic cells, where they participate in the regulation...
The biogenic polyamines, spermidine (Spd) and spermine (Spm), are present at millimolar concentrations in all eukaryotic cells, where they participate in the regulation of vitally important cellular functions. Polyamine analogs and derivatives are a traditional and important instrument for the investigation of the cellular functions of polyamines, enzymes of their metabolism, and the regulation of the biosynthesis of antizyme-a key downregulator of polyamine homeostasis. Here, we describe convenient gram-scale syntheses of a set of -methylated analogs of Spd. The biochemical properties of these compounds and the possibility for the regulation of their activity by moving a methyl group along the polyamine backbone and by changing the stereochemistry of the chiral center(s) are discussed.
Topics: Spermidine; Polyamines; Spermine; Biogenic Polyamines; Homeostasis
PubMed: 37371496
DOI: 10.3390/biom13060916 -
Autophagy Mar 2020Spermidine, a polyamine that induces macroautophagy/autophagy, exhibits anti-aging properties. It is thought that these properties of spermidine are primarily due to its...
Spermidine, a polyamine that induces macroautophagy/autophagy, exhibits anti-aging properties. It is thought that these properties of spermidine are primarily due to its ability to modulate autophagy, but the mechanistic details were hitherto unclear. Studying the effects of spermidine on B lymphocytes, Zhang uncover the molecular mechanism that places spermidine at the crossroads of autophagy and immune senescence. Their work highlights the role of spermidine as an anti-aging metabolite that exerts its effects through the translational control of autophagy. EIF5A, eukaryotic translation initiation factor 5A; HC, hematopoietic cell; ODC1, ornithine decarboxylase 1; PBMCs, peripheral blood mononuclear cells.
Topics: Autophagy; B-Lymphocytes; Cellular Senescence; Leukocytes, Mononuclear; Polyamines; Spermidine
PubMed: 31795807
DOI: 10.1080/15548627.2019.1698210 -
International Journal of Molecular... Aug 2022Studies of human semen in cell or tissue culture are hampered by the high cytotoxic activity of this body fluid. The components responsible for the cell damaging...
Studies of human semen in cell or tissue culture are hampered by the high cytotoxic activity of this body fluid. The components responsible for the cell damaging activity of semen are amine oxidases, which convert abundant polyamines, such as spermine or spermidine in seminal plasma into toxic intermediates. Amine oxidases are naturally present at low concentrations in seminal plasma and at high concentrations in fetal calf serum, a commonly used cell culture supplement. Here, we show that, in the presence of fetal calf serum, seminal plasma, as well as the polyamines spermine and spermidine, are highly cytotoxic to immortalized cells, primary blood mononuclear cells, and vaginal tissue. Thus, experiments investigating the effect of polyamines and seminal plasma on cellular functions should be performed with great caution, considering the confounding cytotoxic effects. The addition of the amine oxidase inhibitor aminoguanidine to fetal calf serum and/or the utilization of serum-free medium greatly reduced this serum-induced cytotoxicity of polyamines and seminal plasma in cell lines, primary cells, and tissues and, thus, should be implemented in all future studies analyzing the role of polyamines and semen on cellular functions.
Topics: Guanidines; Humans; Oxidoreductases; Polyamines; Semen; Serum; Serum Albumin, Bovine; Spermidine; Spermine
PubMed: 35955696
DOI: 10.3390/ijms23158563