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Autophagy Feb 2023Impaired mitophagy is a primary pathogenic event underlying diverse aging-associated diseases such as Alzheimer and Parkinson diseases and sarcopenia. Therefore,...
Impaired mitophagy is a primary pathogenic event underlying diverse aging-associated diseases such as Alzheimer and Parkinson diseases and sarcopenia. Therefore, augmentation of mitophagy, the process by which defective mitochondria are removed, then replaced by new ones, is an emerging strategy for preventing the evolvement of multiple morbidities in the elderly population. Based on the scaffold of spermidine (Spd), a known mitophagy-promoting agent, we designed and tested a family of structurally related compounds. A prototypic member, 1,8-diaminooctane (VL-004), exceeds Spd in its ability to induce mitophagy and protect against oxidative stress. VL-004 activity is mediated by canonical aging genes and promotes lifespan and healthspan in . Moreover, it enhances mitophagy and protects against oxidative injury in rodent and human cells. Initial structural characterization suggests simple rules for the design of compounds with improved bioactivity, opening the way for a new generation of agents with a potential to promote healthy aging.
Topics: Aged; Animals; Humans; Caenorhabditis elegans; Mitophagy; Diamines; Autophagy; Oxidative Stress
PubMed: 35579620
DOI: 10.1080/15548627.2022.2078069 -
Applied and Environmental Microbiology Nov 2020Diamines are important monomers for polyamide plastics; they include 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, and 1,6-diaminohexane, among others. With... (Review)
Review
Diamines are important monomers for polyamide plastics; they include 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, and 1,6-diaminohexane, among others. With increasing attention on environmental problems and green sustainable development, utilizing renewable raw materials for the synthesis of diamines is crucial for the establishment of a sustainable plastics industry. Recently, high-performance microbial factories, such as and , have been widely used in the production of diamines. In particular, several synthetic pathways of 1,6-diaminohexane have been proposed based on glutamate or adipic acid. Here, we reviewed approaches for the biosynthesis of diamines, including metabolic engineering and biocatalysis, and the application of bio-based diamines in nylon materials. The related challenges and opportunities in the development of renewable bio-based diamines and nylon materials are also discussed.
Topics: Bacteria; Biocatalysis; Biosynthetic Pathways; Diamines; Metabolic Engineering; Nylons
PubMed: 32978133
DOI: 10.1128/AEM.01972-20 -
Plant, Cell & Environment Jun 2020Biomarker metabolites are of increasing interest in crops since they open avenues for precision agriculture, whereby nutritional needs and stresses can be monitored... (Review)
Review
Biomarker metabolites are of increasing interest in crops since they open avenues for precision agriculture, whereby nutritional needs and stresses can be monitored optimally. Putrescine has the potential to be a useful biomarker to reveal potassium (K ) deficiency. In fact, although this diamine has also been observed to increase during other stresses such as drought, cold or heavy metals, respective changes are comparably low. Due to its multifaceted biochemical properties, several roles for putrescine under K deficiency have been suggested, such as cation balance, antioxidant, reactive oxygen species mediated signalling, osmolyte or pH regulator. However, the specific association of putrescine build-up with low K availability in plants remains poorly understood, and possible regulatory roles must be consistent with putrescine concentration found in plant tissues. We hypothesize that the massive increase of putrescine upon K starvation plays an adaptive role. A distinction of putrescine function from that of other polyamines (spermine, spermidine) may be based either on its specificity or (which is probably more relevant under K deficiency) on a very high attainable concentration of putrescine, which far exceeds those for spermidine and spermine. putrescine and its catabolites appear to possess a strong potential in controlling cellular K and Ca , and mitochondria and chloroplasts bioenergetics under K stress.
Topics: Biological Transport; Biomarkers; Chloroplasts; Potassium; Putrescine; Stress, Physiological
PubMed: 32017122
DOI: 10.1111/pce.13740 -
Molecules (Basel, Switzerland) May 2019Salen ligands are a class of Schiff bases simply obtained through condensation of two molecules of a hydroxyl-substituted aryl aldehyde with an achiral or chiral... (Review)
Review
Salen ligands are a class of Schiff bases simply obtained through condensation of two molecules of a hydroxyl-substituted aryl aldehyde with an achiral or chiral diamine. The prototype salen, or ,'-bis(salicylidene)ethylenediamine has a long history, as it was first reported in 1889, and immediately, some of its metal complexes were also described. Now, the salen ligands are a class of N,N,O,O tetradentate Schiff bases capable of coordinating many metal ions. The geometry and the stereogenic group inserted in the diamine backbone or aryl aldehyde backbone have been utilized in the past to efficiently transmit chiral information in a variety of different reactions. In this review we will summarize the important and recent achievements obtained in stereocontrolled reactions in which Al(salen) metal complexes are employed. Several other reviews devoted to the general applications and synthesis of chromium and other metal salens have already been published.
Topics: Catalysis; Chemistry Techniques, Synthetic; Cycloaddition Reaction; Ethylenediamines; Molecular Structure; Organometallic Compounds; Polymerization; Stereoisomerism; Uridine Diphosphate N-Acetylglucosamine
PubMed: 31052604
DOI: 10.3390/molecules24091716 -
World Journal of Microbiology &... Oct 2022The consumption of foods fraught with histamine can lead to various allergy-like symptoms if the histamine is not sufficiently degraded in the human body. The... (Review)
Review
The consumption of foods fraught with histamine can lead to various allergy-like symptoms if the histamine is not sufficiently degraded in the human body. The degradation occurs primarily in the small intestine, naturally catalyzed by the human diamine oxidase (DAO). An inherent or acquired deficiency in human DAO function causes the accumulation of histamine and subsequent intrusion of histamine into the bloodstream. The histamine exerts its effects acting on different histamine receptors all over the body but also directly in the intestinal lumen. The inability to degrade sufficient amounts of dietary histamine is known as the 'histamine intolerance'. It would be preferable to solve this problem initially by the production of histamine-free or -reduced foods and by the oral supplementation of exogenous DAO supporting the human DAO in the small intestine. For the latter, DAOs from mammalian, herbal and microbial sources may be applicable. Microbial DAOs seem to be the most promising choice due to their possibility of an efficient biotechnological production in suitable microbial hosts. However, their biochemical properties, such as activity and stability under process conditions and substrate selectivity, play important roles for their successful application. This review deals with the advances and challenges of DAOs and other histamine-oxidizing enzymes for their potential application as processing aids for the production of histamine-reduced foods or as orally administered adjuvants to humans who have been eating food fraught with histamine.
Topics: Amine Oxidase (Copper-Containing); Animals; Diamines; Histamine; Humans; Mammals; Oxidation-Reduction; Receptors, Histamine
PubMed: 36208352
DOI: 10.1007/s11274-022-03421-2 -
Nature Communications Aug 2022Molecular conformations induced by the rotation about single bonds play a crucial role in chemical transformations. Revealing the relationship between the conformations...
Molecular conformations induced by the rotation about single bonds play a crucial role in chemical transformations. Revealing the relationship between the conformations of chiral catalysts and the enantiodiscrimination is a formidable challenge due to the great difficulty in isolating the conformers. Herein, we report a chiral catalytic system composed of an achiral catalytically active unit and an axially chiral 1,1'-bi-2-naphthol (BINOL) unit which are connected via a C-O single bond. The two conformers of the catalyst induced by the rotation about the C-O bond, are determined via single-crystal X-ray diffraction and found to respectively lead to the formation of highly important axially chiral 1,1'-binaphthyl-2,2'-diamine (BINAM) and 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN) derivatives in high yields (up to 98%), with excellent enantioselectivities (up to 98:2 e.r.) and opposite absolute configurations. The results highlight the importance of conformational dynamics of chiral catalysts in asymmetric catalysis.
Topics: Catalysis; Crystallography, X-Ray; Diamines; Molecular Conformation
PubMed: 35961985
DOI: 10.1038/s41467-022-32432-8 -
Contraception Mar 2013A non-hormonal male contraceptive is a contraceptive that does not involve the administration of hormones or hormone blockers. This review will focus on the use of... (Review)
Review
A non-hormonal male contraceptive is a contraceptive that does not involve the administration of hormones or hormone blockers. This review will focus on the use of lonidamine derivatives and inhibitors of retinoic acid biosynthesis and function as approaches to male non-hormonal contraception. Two current lonidamine derivatives, adjudin and H2-gamendazole, are in development as male contraceptives. These potent anti-spermatogenic compounds impair the integrity of the apical ectoplasmic specialization, resulting in premature spermiation and infertility. Another approach to male contraceptive development is the inhibition of retinoic acid in the testes, as retinoic acid signaling is necessary for spermatogenesis. The administration of the retinoic acid receptor antagonist BMS-189453 reversibly inhibits spermatogenesis in mice. Similarly, oral dosing of WIN 18,446, which inhibits testicular retinoic acid biosynthesis, effectively contracepts rabbits. Hopefully, one of these approaches to non-hormonal male contraception will prove to be safe and effective in future clinical trials.
Topics: Animals; Contraception; Contraceptive Agents, Male; Diamines; Humans; Hydrazines; Indazoles; Male; Retinoids; Tretinoin
PubMed: 22995542
DOI: 10.1016/j.contraception.2012.08.016 -
The Journal of Organic Chemistry Aug 2021Novel 1,2-diamines based on the mefloquine scaffold prepared in enantiomerically pure forms resemble 9-amino- alkaloids. Most effectively, 11-aminomefloquine with an...
Novel 1,2-diamines based on the mefloquine scaffold prepared in enantiomerically pure forms resemble 9-amino- alkaloids. Most effectively, 11-aminomefloquine with an configuration was obtained by conversion of 11-alcohol into azide and hydrogenation. Alkylation of a secondary amine unit was needed to arrive at diastereomeric -11-aminomefloquine and to introduce diversity. Most of the substitution reactions of the hydroxyl group to azido group proceeded with net retention of the configuration and involved actual aziridine or plausible aziridinium ion intermediates. Enantiomerically pure products were obtained by the resolution of either the initial mefloquine or one of the final products. The evaluation of the efficacy of the obtained vicinal diamines in enantioselective transformations proved that -11-aminomefloquine is an effective catalyst in the asymmetric Michael addition of nitromethane to cyclohexanone (up to 96.5:3.5 er) surpassing -aminoquinine in terms of selectivity.
Topics: Amines; Diamines; Mefloquine; Molecular Structure; Stereoisomerism
PubMed: 34314190
DOI: 10.1021/acs.joc.1c01316 -
Nature Aug 2021The substitution of an alkyl electrophile by a nucleophile is a foundational reaction in organic chemistry that enables the efficient and convergent synthesis of organic...
The substitution of an alkyl electrophile by a nucleophile is a foundational reaction in organic chemistry that enables the efficient and convergent synthesis of organic molecules. Although there has been substantial recent progress in exploiting transition-metal catalysis to expand the scope of nucleophilic substitution reactions to include carbon nucleophiles, there has been limited progress in corresponding reactions with nitrogen nucleophiles. For many substitution reactions, the bond construction itself is not the only challenge, as there is a need to control stereochemistry at the same time. Here we describe a method for the enantioconvergent substitution of unactivated racemic alkyl electrophiles by a ubiquitous nitrogen-containing functional group, an amide. Our method uses a photoinduced catalyst system based on copper, an Earth-abundant metal. This process for asymmetric N-alkylation relies on three distinct ligands-a bisphosphine, a phenoxide and a chiral diamine. The ligands assemble in situ to form two distinct catalysts that act cooperatively: a copper/bisphosphine/phenoxide complex that serves as a photocatalyst, and a chiral copper/diamine complex that catalyses enantioselective C-N bond formation. Our study thus expands enantioselective N-substitution by alkyl electrophiles beyond activated electrophiles (those bearing at least one sp- or sp-hybridized substituent on the carbon undergoing substitution) to include unactivated electrophiles.
Topics: Amides; Bromides; Carbon; Catalysis; Copper; Cyclization; Diamines; Ligands; Nitrogen; Phosphines; Photochemistry
PubMed: 34182570
DOI: 10.1038/s41586-021-03730-w -
Organic Letters Feb 2021A cobalt-catalyzed method for the C(sp)-C(sp) Suzuki-Miyaura cross coupling of aryl boronic esters and alkyl bromides is described. Cobalt-ligand combinations were...
A cobalt-catalyzed method for the C(sp)-C(sp) Suzuki-Miyaura cross coupling of aryl boronic esters and alkyl bromides is described. Cobalt-ligand combinations were assayed with high-throughput experimentation, and cobalt(II) sources with -,'-dimethylcyclohexane-1,2-diamine (DMCyDA, L) produced optimal yield and selectivity. The scope of this transformation encompassed steric and electronic diversity on the aryl boronate nucleophile as well as various levels of branching and synthetically valuable functionality on the electrophile. Radical trap experiments support the formation of electrophile-derived radicals during catalysis.
Topics: Bromides; Catalysis; Cobalt; Diamines; Esters; Ligands; Molecular Structure
PubMed: 32996312
DOI: 10.1021/acs.orglett.0c02934