32213-95-9Relevant academic research and scientific papers
Antioxidant activity, synthesis and characterization of Schiff base ligand 'asasp' and metal complexes
Ozdemir, Mecit,Sonmez, Mehmet
, p. 7009 - 7015 (2014)
In the present work, the synthesis and structural characterization of a novel Schiff base ligand derived from 2-acetyl pyridine and L-aspartic acid dimethyl ester and its metal complexes have been reported. All the synthesized compounds were characterized by using various spectral techniques like ESI-MS, FT-IR, 1H NMR, 13C NMR, UV-visible spectra, elemental analysis and ICP-OES analyses. The ligand and metal ions reacted to form in the 2:1 or 1:1 (M:L) ratio as found from the elemental analyses and the general stoichiometry was determined [L(Cu)2(AcO)4] and [LM(H2O)2]2Cl·nH2O where M = Co(II), Ni(II), Ni(II) and L = asasp and n = 1 or 2. On the basis of nalytical data, a possible structure for the copper(II) complex is tetrahedral and those for the Co(II), Ni(II) and Mn(II) complexes are ctahedral. The ligand and its metal complexes were tested for their possible antioxidant potentials. Comparison of antioxidant assays ere investigated by using two reference molecules, vitamin C and quercetin. The complexes showed significant activities in these in vitro ntioxidant assays compared to the reference (quercetin and vitamin C) and Ni(II)-complex exhibited a promising antioxidant activity.
2-(2-Hydroxyethyl)piperazine derivatives as potent human carbonic anhydrase inhibitors: Synthesis, enzyme inhibition, computational studies and antiglaucoma activity
Chiaramonte, Niccolò,Angeli, Andrea,Sgambellone, Silvia,Bonardi, Alessandro,Nocentini, Alessio,Bartolucci, Gianluca,Braconi, Laura,Dei, Silvia,Lucarini, Laura,Teodori, Elisabetta,Gratteri, Paola,Wünsch, Bernhard,Supuran, Claudiu T.,Romanelli, Maria Novella
, (2021/12/17)
Targeting Carbonic Anhydrases (CAs) represents a strategy to treat several diseases, from glaucoma to cancer. To widen the structure-activity relationships (SARs) of our series of piperazines endowed with potent human carbonic anhydrase (hCA) inhibition, a new series of chiral piperazines carrying a (2-hydroxyethyl) group was prepared. The Zn-binding function, the 4-sulfamoylbenzoyl moiety, was connected to one piperazine N-atom, while the other nitrogen was decorated with alkyl substituents. In analogy to the approach used for the synthesis of the previously reported series, the preparation of the new compounds started with (R)- and (S)-aspartic acid. A partial racemization occurred during the synthesis. In order to overcome this problem, other chemical strategies were investigated. The inhibitory activity of the new polar derivatives against four hCAs isoforms I, II, IV and IX using a stopped flow CO2 hydrase assay was determined. Some compounds showed potency in the nanomolar range and a preference for inhibiting hCA IX.
Ribose conversion with amino acids into pyrraline platform chemicals-expeditious synthesis of diverse pyrrole-fused alkaloid compounds
Cho, Soohyeon,Gu, Lina,In, Ik Joon,Kim, Hakwon,Koo, Sangho,Lee, Taehoon,Wu, Bo
, p. 31511 - 31525 (2021/11/30)
One-pot conversion of sustainable d-ribose with l-amino acid, methyl esters produced pyrrole-2-carbaldehydes 5 in reasonable yields (32-63%) under pressurized conditions of 2.5 atm at 80 °C. The value-added pyrraline compounds 5 as platform chemicals were utilized for quick installation of poly-heterocyclic cores for the development of pyrrole-motif natural and artificial therapeutic agents. A pyrrole-fused piperazin-2-one scaffold 6 was prepared by reductive amination of pyrralines 5 with benzylamine. While further cyclization of pyrralines 5 with ethane-1,2-diamine produced pyrrolo-piperazin-2-ones 7 with an extra imidazolidine ring, the reaction with 2-amino alcohols derived from natural l-amino acids, alanine, valine, and phenylalanine, respectively provided pyrrolo-piperazin-2-ones 8, 9, and 10 with oxazolidine as the third structural core. Cell viability and an anti-inflammatory effect of the synthesized compounds were briefly tested by the MTT method and the Griess assay, among which 8h and 10g exhibited significant anti-inflammatory effects with negligible cell toxicity.
Substrate Engineering in Lipase-Catalyzed Selective Polymerization of d -/ l -Aspartates and Diols to Prepare Helical Chiral Polyester
Zhang, Yu,Xia, Bo,Li, Yanyan,Lin, Xianfu,Wu, Qi
, p. 918 - 926 (2021/02/01)
The synthesis of optically pure polymers is one of the most challenging tasks in polymer chemistry. Herein, Novozym 435 (Lipase B from Candida antarctica, immobilized on Lewatit VP OC 1600)-catalyzed polycondensation between d-/l-aspartic acid (Asp) diester and diols for the preparation of helical chiral polyesters was reported. Compared with d-Asp diesters, the fast-reacting l-Asp diesters easily reacted with diols to provide a series of chiral polyesters containing N-substitutional l-Asp repeating units. Besides amino acid configuration, N-substituent side chains and the chain length of diols were also investigated and optimized. It was found that bulky acyl N-substitutional groups like N-Boc and N-Cbz were more favorable for this polymerization than small ones probably due to competitively binding of these small acyl groups into the active site of Novozym 435. The highest molecular weight can reach up to 39.5 × 103 g/mol (Mw, D = 1.64). Moreover, the slow-reacting d-Asp diesters were also successfully polymerized by modifying the substrate structure to create a "nonchiral"condensation environment artificially. These enantiocomplementary chiral polyesters are thermally stable and have specific helical structures, which was confirmed by circular dichroism (CD) spectra, scanning electron microscope (SEM), and molecular calculation.
Conformationally rigid pyrazoloquinazoline α-amino acids: One- And two-photon induced fluorescence
Bell, Jonathan D.,Harkiss, Alexander H.,Nobis, David,Malcolm, Eilidh,Knuhtsen, Astrid,Wellaway, Christopher R.,Jamieson, Andrew G.,Magennis, Steven W.,Sutherland, Andrew
supporting information, p. 1887 - 1890 (2020/02/22)
The synthesis and photophysical properties of a new class of α-amino acid bearing a rigid pyrazoloquinazoline chromophore are described. Confromational constraint of the amino acid side-chains resulted in high emission quantum yields, while the demonstration of two-photon-induced fluorescence via near-IR excitation signifies their potential for sensitive bioimaging applications.
Synthesis of (+)- and (?)-Geissman-Waiss lactone from chiral sulfonium salts
López-González, Ricardo,Gnecco, Dino,Juárez, Jorge R.,Orea, María L.,Gómez-Calvario, Victor,Bernès, Sylvain,Aparicio, David M.,Terán, Joel L.
supporting information, (2020/02/18)
A novel series of chiral cyclic zwitterionic pyrrolidinone type intermediates was prepared via regioselective 5-exo-trig-ring-closure of the corresponding chiral sulfonium salts. This synthetic strategy allowed the rapid non-racemic synthesis of the Geissman-Waiss lactone in six steps and 35% overall yield.
Design, Synthesis, and Pharmacological Characterization of a Neutral, Non-Prodrug Thrombin Inhibitor with Good Oral Pharmacokinetics
Hillisch, Alexander,Gericke, Kersten M.,Allerheiligen, Swen,Roehrig, Susanne,Schaefer, Martina,Tersteegen, Adrian,Schulz, Simone,Lienau, Philip,Gnoth, Mark,Puetter, Vera,Hillig, Roman C.,Heitmeier, Stefan
, p. 12574 - 12594 (2020/11/13)
Despite extensive research on small molecule thrombin inhibitors for oral application in the past decades, only a single double prodrug with very modest oral bioavailability has reached human therapy as a marketed drug. We have undertaken major efforts to identify neutral, non-prodrug inhibitors. Using a holistic analysis of all available internal data, we were able to build computational models and apply these for the selection of a lead series with the highest possibility of achieving oral bioavailability. In our design, we relied on protein structure knowledge to address potency and identified a small window of favorable physicochemical properties to balance absorption and metabolic stability. Protein structure information on the pregnane X receptor helped in overcoming a persistent cytochrome P450 3A4 induction problem. The selected compound series was optimized to a highly potent, neutral, non-prodrug thrombin inhibitor by designing, synthesizing, and testing derivatives. The resulting optimized compound, BAY1217224, has reached first clinical trials, which have confirmed the desired pharmacokinetic properties.
Development of l-Amino-Acid-Based Hydroxyl Functionalized Biodegradable Amphiphilic Polyesters and Their Drug Delivery Capabilities to Cancer Cells
Saxena, Sonashree,Jayakannan, Manickam
, p. 171 - 187 (2019/11/11)
Hydroxyl-functionalized amphiphilic polyesters based on l-amino acid bioresources were designed and developed, and their nanoassemblies were explored as intracellular enzyme-biodegradable scaffolds for delivering anticancer drugs and fluorophores to cancer cells. To accomplish this task, acetal-masked multifunctional dicarboxylic ester monomer from l-aspartic acid was tailor-made, and it was subjected to solvent-free melt transesterification polycondensation with commercial diols to produce acetal-functionalized polyesters. Acid-catalyzed postpolymerization deprotection of these acetal-polyesters produced amphiphilic hydroxyl-functionalized polyesters. The amphiphilic polyesters were self-assembled in aqueous medium to produce nanoparticles of size 200 nm. Wide ranges of both water-soluble and water-insoluble anticancer drugs such as doxorubicin (DOX), camptothecin (CPT), and curcumin (CUR) and fluorophores such as Nile red (NR), Rose Bengal (RB), and Congo red (CR) were encapsulated in hydroxyl polyesters nanoparticles. In vitro drug release studies revealed that the aliphatic polyester backbone underwent lysosomal enzymatic-biodegradation to release the loaded cargoes at the intracellular compartments. Lysotracker-assisted live-cell confocal microscopy studies further confirmed the colocalization of the polymer nanoscaffolds in the lysosomes and supported their enzymatic-biodegradation for drug delivery. In vitro cytotoxicity studies showed that the nascent polymers were not toxic, whereas their anticancer drug-loaded nanoparticles exhibited excellent cell killing in cervical cancer (HeLa) cell lines. The drug-loaded (CPT, CUR, and DOX) and the fluorophore-loaded (NR, RB, and CR) polymer nanoparticles were highly luminescent; thus, the encapsulated polymer nanoparticles enabled the multiple color-tunable bioimaging in cancer cells in the entire visible region from blue to deep red. Time-dependent live-cell confocal microscopy studies established that the cellular uptake of drugs and fluorophores was 5 to 10-fold higher while they were delivered from the hydroxyl polyester platform. The hydroxyl polyester nanocarrier design strategy opens up new opportunities in drug delivery to cancer cells from a biodegradable polymer platform based on l-amino acids.
Development of bisubstrate analog inhibitors of aspartate N-acetyltransferase, a critical brain enzyme
Mutthamsetty, Vinay,Dahal, Gopal P.,Wang, Qinzhe,Viola, Ronald E.
, p. 48 - 57 (2019/11/25)
Canavan disease (CD) is a fatal leukodystrophy caused by mutations in the aspA gene coding for the enzyme aspartoacylase. Insufficient catalytic activity by this enzyme leads to the accumulation of its substrate, N-acetyl-l-aspartate (NAA), and diminished production of acetate in brain oligodendrocytes of patients with CD. There is growing evidence that this accumulation of NAA is the cause of many of the developmental defects observed in these patients. NAA is produced in the brain by a transacetylation reaction catalyzed by aspartate N-acetyltransferase (ANAT), and this membrane-associated enzyme has recently been purified as a soluble maltose binding protein fusion. Designing selective inhibitors against ANAT has the potential to slow the accumulation of NAA and moderate these developmental defects, and this is the goal of this project. Several bisubstrate analog inhibitors of ANAT have been synthesized that have achieved nanomolar level binding affinities against this enzyme. Truncated versions and fragments of these bisubstrate analog inhibitors have identified the essential structural elements needed for high binding affinity. More drug-like versions of these inhibitors can now be built, based on these essential core structures.
Unsaturation and Polar Head Effect on Gelation, Bioactive Release, and Cr/Cu Removal Ability of Glycolipids
Bojja, Sreedhar,Holey, Snehal Ashokrao,Nayak, Rati Ranjan,Sekhar, Kanaparedu P. C.,Swain, Deepak Kumar
, p. 3080 - 3088 (2020/08/06)
Designing of multifunctional soft and smart materials from natural sources is a useful strategy for producing safer chemicals having potential applications in biomedical research and pharmaceutical industries. Herein, eight glycolipids with variation in unsaturation of hydrophobic tail and polar headgroup size were designed. The effect of unsaturation in the tail group and headgroup size on gelation ability, and mechanical and thermal stability of glycolipid hydro/organogels was studied to understand structure and property relationship. Glycolipids are functional amphiphilic molecules having potential applications in the field of drug delivery and metal removal. The encapsulation capacity and kinetic release behavior of hydrophobic/hydrophilic bioactives like curcumin/riboflavin from the hydrophobic/hydrophilic pockets of glycolipids hydro/organogels was examined. A significant observation was that the glucamine moiety of the glycolipid headgroup plays a vital role in removal of Cr and Cu from oil/water biphasic systems. Typical functions of the glycolipid hydrogels are metal chelation and enzyme-triggered release behavior, enabled them as promising material for Cr, Cu removal from edible oils and controlled release of water soluble/insoluble bioactives.
