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Parasites & Vectors Jun 2016Strongyloidiasis is a parasitic disease widely present in tropical and subtropical areas. Strongyloides stercoralis represents the main species that infects human...
BACKGROUND
Strongyloidiasis is a parasitic disease widely present in tropical and subtropical areas. Strongyloides stercoralis represents the main species that infects human beings. Ivermectin is the current drug of choice; however, issues related with treatment failure in patients with diabetes or infected with T-lymphotropic virus-1 make the identification of new molecules for alternative treatment a priority. In the present study, the activity of sphingosine-related aminoalcohol and diamine were evaluated against Strongyloides venezuelensis third-stage larva (L3) cultures and experimental infections in mice.
METHODS
The efficacy of each compound against L3 was assessed using both XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay and microscopic observation with concentrations ranging from 1 to 350 μM. Cytotoxicity was evaluated using J774.2 macrophage cell line and XTT assay. Lethal concentration 50 (LC50), selectivity index (SI) and structure-activity relationships were established. The activity compounds 4 (2-(ethylamino) hexadecan-1-ol), 6 (2-(butylamino) hexadecan-1-ol), 17 (tert-butyl N-(1-aminododecan-2-yl) carbamate) and 18 (tert-butyl N-(1-aminohexadecan-2-yl) carbamate) were further assessed against experimental S. venezuelensis infections in CD1 mice measuring reductions in the numbers of parthenogenetic females and egg passed in faeces. Mice were infected with 3,000 L3 and treated with 20 mg/kg/day for five days.
RESULTS
In the screening study of 15 aminoalcohols [lauryl (n = 9); palmityl (n = 13); stearyl (n = 15) and alcohol derivatives], the presence of a palmitol chain was associated with the highest efficacy against L3 (LC50 31.9-39.1 μM). Alkylation of the 2-amino group with medium size fragments as ethyl or n-butyl showed the best larvicidal activity. The dialkylation did not improve efficacy. Aminoalcohols 4 and 6 showed the highest SI (1.5 and 1.6, respectively). With respect to diamine derivative compounds, a chain size of sixteen carbon atoms (palmitoyl chain, n = 13), and the alkylation of the 2-amino group with medium-sized fragments, were associated with the highest lethal activities. The presence of carbamoyl group in diamines 17 and 18 yielded high SI (1.7 and 1.4, respectively). Infected mice treated with aminoalcohol 6 showed reduction in parthenogenetic females (59 %) and eggs in faeces (51 %).
CONCLUSIONS
These results support the potentiality of aminoalcohol and diamine sphingosine-related compounds as suitable prototypes for developing new promising drugs against strongyloidiasis.
Topics: Amino Alcohols; Animals; Anthelmintics; Diamines; Male; Mice; Molecular Structure; Rats; Strongyloides; Strongyloidiasis; Structure-Activity Relationship
PubMed: 27353595
DOI: 10.1186/s13071-016-1648-5 -
Molecules (Basel, Switzerland) Jun 2022The condensation of aromatic dialdehydes with chiral diamines, such as 1,2--diaminocyclohexane, leads to various enantiopure or -type macrocyclic Schiff bases, including... (Review)
Review
The condensation of aromatic dialdehydes with chiral diamines, such as 1,2--diaminocyclohexane, leads to various enantiopure or -type macrocyclic Schiff bases, including [2 + 2], [3 + 3], [4 + 4], [6 + 6] and [8 + 8] condensation products. Unlike most cases of macrocycle synthesis, the [3 + 3] macrocycles of this type are sometimes obtained in high yields by direct condensation without a metal template. Macrocycles of other sizes from this family can often be selectively obtained in high yields by a suitable choice of metal template, solvent, or chirality of the building blocks. In particular, the application of a cadmium(II) template results in the expansion of the [2 + 2] macrocycles into giant [6 + 6] and [8 + 8] macrocycles. These imine macrocycles can be reduced to the corresponding macrocyclic amines which can act as hosts for the binding of multiple cations or multiple anions.
Topics: Amines; Diamines; Imines; Macrocyclic Compounds; Metals; Molecular Structure; Stereoisomerism
PubMed: 35807342
DOI: 10.3390/molecules27134097 -
Biomacromolecules Aug 2020A series of cationic polypeptide imidazolium conjugates were prepared by ring-opening polymerization (ROP) of γ-4-(3-chloropropoxycarbonyl)benzyl-- glutamic acid-based...
A series of cationic polypeptide imidazolium conjugates were prepared by ring-opening polymerization (ROP) of γ-4-(3-chloropropoxycarbonyl)benzyl-- glutamic acid-based -carboxyanhydride (CPBLG-NCA) initiated by various mono- or diamine initiators and subsequent side-chain modification with high grafting efficiency. Rapid and controlled ROP was achieved by polymerizing CPBLG-NCA in a dichloromethane/NaHCO/HO solvent mixture with the amine initiators. The resulting polypeptides bearing imidazolium iodide pendants showed reversible upper critical solution temperature (UCST)-type thermoresponsive properties in both ethanol and DI water while the polypeptides with tetrafluoroborate counter-anions showed a UCST in phosphate buffer saline (PBS). The cloud point temperature () in ethanol and aqueous solutions can be tuned by both molecular weight and the end- or linkage-groups in the main chain. The cationic polypeptides showed good antibacterial activity against and low hemolysis. Our results provide a facile and rapid ROP strategy to develop new families of stimuli-responsive polypeptides with tunable properties as well as antibacterial polypeptides with optimized selectivity.
Topics: Diamines; Molecular Weight; Peptides; Polymerization; Temperature
PubMed: 32597642
DOI: 10.1021/acs.biomac.0c00953 -
Macromolecular Rapid Communications Jan 2023Innovative dielectric materials with high-temperature resistance and outstanding dielectric properties have attracted tremendous attention in advanced electronical...
Innovative dielectric materials with high-temperature resistance and outstanding dielectric properties have attracted tremendous attention in advanced electronical fields. Polyimide(PI) is considered a promising candidate for the modern electronic industry due to its excellent dielectric properties and comprehensive properties. However, the limited-adjustable range of dielectric constant and the difficulty to obtain a high dielectric constant restrict the application of PI as high dielectric materials. Herein, a novel diamine monomer (2,2'-bis((methylsulfonyl)methyl)-[1,1'-biphenyl]-4,4'-diamine (BSBPA)) containing a rigid biphenyl structure and high dipolar sulfonyl pendant groups is designed for high dielectric polyimides. The rigid biphenyl and polar sulfonyl pendant groups can reasonably optimize the molecular structure and orientational polarization of polyimides to improve their dielectric properties and thermal properties. Moreover, the effect of different bridge linkages on the dielectric properties is studied by using the different dianhydrides. Thus, the PI-BSBPA films especially the DSDA-BSBPA film (DSDA: 3,3',4,4'-diphenylsulfonetetracarboxylic dianhydride) achieve great thermal properties (T of 377 °C and T of 358 °C) and excellent dielectric properties (6.95 at 1 kHz) along with high discharged energy density of 5.25 J cm and charge-discharge efficiency of 90%. The collaborative control of main-chain and side-chain engineering is effective to endow the polyimides with high-temperature tolerance and high dielectric performance.
Topics: Temperature; Biphenyl Compounds; Diamines; Electronics
PubMed: 36125201
DOI: 10.1002/marc.202200639 -
Biotechnology Advances 2023Recently, bio-based manufacturing processes of value-added platform chemicals and polymers in biorefineries using renewable resources have extensively been developed for... (Review)
Review
Recently, bio-based manufacturing processes of value-added platform chemicals and polymers in biorefineries using renewable resources have extensively been developed for sustainable and carbon dioxide (CO) neutral-based industry. Among them, bio-based diamines, aminocarboxylic acids, and diacids have been used as monomers for the synthesis of polyamides having different carbon numbers and ubiquitous and versatile industrial polymers and also as precursors for further chemical and biological processes to afford valuable chemicals. Until now, these platform bio-chemicals have successfully been produced by biorefinery processes employing enzymes and/or microbial host strains as main catalysts. In this review, we discuss recent advances in bio-based production of diamines, aminocarboxylic acids, and diacids, which has been developed and improved by systems metabolic engineering strategies of microbial consortia and optimization of microbial conversion processes including whole cell bioconversion and direct fermentative production.
Topics: Nylons; Diamines; Polymers; Metabolic Engineering; Fermentation
PubMed: 36462631
DOI: 10.1016/j.biotechadv.2022.108070 -
ChemMedChem May 2019DAPT is a potent γ-secretase (GS) inhibitor that blocks the production of short amyloid-β (Aβ) peptides. Aggregation and oligomerization of Aβ peptides have been...
DAPT is a potent γ-secretase (GS) inhibitor that blocks the production of short amyloid-β (Aβ) peptides. Aggregation and oligomerization of Aβ peptides have been associated with the development and progression of Alzheimer's disease. A recent cryo-electron microscopy density map disclosed DAPT binding at the GS active site. In this study, we employed the density map data to assign a possible binding pose of DAPT to characterize its dynamic behavior through different molecular dynamics simulation approaches. Our simulations showed a high preference of DAPT for the intramembrane region of the protein and that its entry site is located between TM2 and TM3 of PS1. DAPT interaction with the active site led to a decreased flexibility of key PS1 regions related to the recognition and internalization of GS substrates. Moreover, our study showed that the proximity of DAPT to the catalytic aspartic acids should be able to modify its protonation states, preventing the enzyme from reaching its active form. These results provide valuable information toward understanding the molecular mechanism of a GS inhibitor for the development of novel Alzheimer's disease treatments.
Topics: Amino Acid Sequence; Amyloid Precursor Protein Secretases; Amyloid beta-Peptides; Aspartic Acid; Catalytic Domain; Diamines; Enzyme Inhibitors; Molecular Dynamics Simulation; Protein Binding; Protein Conformation; Thermodynamics; Thiazoles
PubMed: 30925201
DOI: 10.1002/cmdc.201900106 -
Bioorganic & Medicinal Chemistry Aug 2015Visceral leishmaniasis is a neglected parasitic disease that has a high fatality rate in the absence of treatment. New drugs that are inexpensive, orally active, and...
Visceral leishmaniasis is a neglected parasitic disease that has a high fatality rate in the absence of treatment. New drugs that are inexpensive, orally active, and effective could be useful tools in the fight against this disease. We previously showed that N(2),N(4)-disubstituted quinazoline-2,4-diamines displayed low- to sub-micromolar potency against intracellular Leishmania, and lead compound N(4)-(furan-2-ylmethyl)-N(2)-isopropyl-7-methylquinazoline-2,4-diamine (4) exhibited modest efficacy in an acute murine model of visceral leishmaniasis. In the present work, thirty-one N(2),N(4)-disubstituted quinazoline-2,4-diamines that had not previously been examined for their antileishmanial activity were evaluated for their potency and selectivity against Leishmania donovani, the causative parasite of visceral leishmaniasis. Quinazoline-2,4-diamines with aromatic substituents at both N(2) and N(4) exhibited potent in vitro antileishmanial activity but relatively low selectivity, while compounds substituted with small alkyl groups at either N(2) or N(4) generally showed lower antileishmanial potency but were less toxic to a murine macrophage cell line. Based on their in vitro antileishmanial potency, N(4)-benzyl-N(2)-(4-chlorobenzyl)quinazoline-2,4-diamine (15) and N(2)-benzyl-N(4)-isopropylquinazoline-2,4-diamine (40) were selected for in vivo evaluation of their pharmacokinetic and antileishmanial properties. While 15 displayed a longer plasma half-life and a greater area under the curve than 40, both compounds showed low efficacy in an acute murine visceral leishmaniasis model. Although the present study did not identify new quinazoline-2,4-diamines with promising in vivo efficacy, the reduced in vitro toxicity of derivatives bearing small alkyl groups at either N(2) or N(4) may provide clues for the design of safe and effective antileishmanial quinazolines.
Topics: Animals; Antiprotozoal Agents; Diamines; Humans; Leishmania donovani; Leishmaniasis, Visceral; Mice; Mice, Inbred BALB C; Neglected Diseases; Quinazolines; Structure-Activity Relationship
PubMed: 25749014
DOI: 10.1016/j.bmc.2015.02.020 -
Biomacromolecules Jan 2023The reductive amination of dialdehyde cellulose (DAC) with 2-picoline borane was investigated for its applicability in the generation of bioderived thermoplastics. Five...
The reductive amination of dialdehyde cellulose (DAC) with 2-picoline borane was investigated for its applicability in the generation of bioderived thermoplastics. Five primary amines, both aliphatic and aromatic, were introduced to the cellulose backbone. The influences of the side chains on the course of the reaction were examined by various analytical techniques with microcrystalline cellulose as a model compound. The obtained insights were transferred to a 39%-oxidized softwood kraft pulp to study the thermal properties of thereby generated high-molecular-weight thermoplastics. The number-average molecular weights () of the diamine celluloses, ranging from 60 to 82 kD, were investigated by gel permeation chromatography. The diamine celluloses exhibited glass transition temperatures () from 71 to 112 °C and were stable at high temperatures. Diamine cellulose generated from aniline and DAC showed the highest conversion, the highest (112 °C), and a narrow molecular weight distribution ( of 1.30).
Topics: Amination; Amines; Cellulose; Diamines
PubMed: 36542819
DOI: 10.1021/acs.biomac.2c01022 -
Chemical Communications (Cambridge,... Jan 2023Vicinal diamines are an important structural motif in bioactive natural products and pharmaceutical intermediates. Herein, an environmentally friendly and efficient...
Vicinal diamines are an important structural motif in bioactive natural products and pharmaceutical intermediates. Herein, an environmentally friendly and efficient electrochemical approach to azidoacetamides, as one variant of vicinal diamines, has been developed. This reaction features mild conditions and broad substrate scope, without the use of any chemical oxidant or transition-metal catalysts. The obtained vicinal azidoacetamides could be conveniently converted into various other vicinal diamine derivatives.
Topics: Molecular Structure; Diamines; Catalysis
PubMed: 36514900
DOI: 10.1039/d2cc06246a -
Steroids Jul 2019Two series of cholestane-based diamines (1,2 and 1,3) were synthesized using simple and efficient procedures. The convenient substrates for these syntheses were... (Review)
Review
Two series of cholestane-based diamines (1,2 and 1,3) were synthesized using simple and efficient procedures. The convenient substrates for these syntheses were cholesteryl mesylate and tosylate, which were converted to appropriate amines via easily obtained azides. The final diamines were prepared using a substitution reaction with bromoacetonitrile (in the case of 1,2-diamines) or condensation with acrylonitrile (in the case of 1,3-diamines), followed by the reduction of intermediate aminonitriles. Furthermore, the other two amines were synthesized from 16-dehydropregnenolone acetate using aza-Michael addition as a key step. Some of the diamines were subjected to complexation reactions with KPtCl to form steroidal analogs of cisplatin. The synthetic methods tested in this work will allow us to prepare other cisplatin derivatives based on steroids showing anticancer properties themselves.
Topics: Coordination Complexes; Diamines; Ions; Ligands; Molecular Structure; Transition Elements
PubMed: 30738072
DOI: 10.1016/j.steroids.2019.02.001