51411-04-2 Usage
Description
Alrestatin, a naturally occurring compound, is an inhibitor of aldose reductase, an enzyme involved in the polyol pathway. It has been demonstrated to effectively inhibit aldose reductase prepared and purified from the human brain. Alrestatin is known for its potential therapeutic applications in various health conditions related to aldose reductase overactivity.
Source:
Alrestatin is typically derived from the mushroom Antrodia camphorata, which is native to Taiwan and has been traditionally used in Chinese medicine.
Production Methods:
The production of alrestatin involves the extraction and purification processes from the fruiting bodies or mycelium of the Antrodia camphorata mushroom.
Uses
Used in Pharmaceutical Industry:
Alrestatin is used as an enzyme inhibitor for targeting aldose reductase, which plays a significant role in the development of diabetic complications, such as cataracts, neuropathy, and retinopathy. By inhibiting aldose reductase, Alrestatin can potentially reduce the severity of these complications and improve the quality of life for patients with diabetes.
Used in Research Applications:
In the field of scientific research, Alrestatin is utilized as a research tool to study the role of aldose reductase in various pathological conditions. It helps researchers understand the enzyme's function and its contribution to the development of diseases, which can lead to the discovery of new therapeutic strategies and treatments.
Used in Drug Development:
Alrestatin serves as a lead compound in the development of new drugs aimed at treating conditions related to aldose reductase overactivity. Its inhibitory properties make it a valuable starting point for designing and synthesizing novel compounds with improved efficacy and selectivity.
Originator
Alrestatin,BIOMOL
Manufacturing Process
1,3-Dioxo-1H-benz[de]isoquinoline-2(3H)-acetic acid:
1,8-Naphthalic acid anhydride (110 g, 0.556 mole), glycine (48 g, 0.64 mole)
and dimethylformamide (750 ml) are heated and stirred at reflux for 2 hr. The
homogeneous dark solution is cooled to about 100°C and 750 ml of hot water
is added slowly to the stirred solution. The reaction mixture is cooled and
allowed to stand in a refrigerator for 16 hr. The precipitate is collected and
recrystallized from ethanol, using decolorizing charcoal, to give the title
compound, MP: 271°-272°C.
In practice it is usually used as sodium salt.
Biological Activity
Specific inhibitor of aldose reductase (IC 50 = 148 μ M). Attenuates glucose-induced angiotensin II production in rat vascular smooth muscle in vitro .
Enzyme inhibitor
This aldose reductase inhibitor and drug (FWfree-acid = 255.23 g/mol; CAS 51411-04-2), also known as 1,3-dioxo-1H-benz[de]isoquinoline-2(3H)- acetic acid) suppresses diabetes-associated, osmotic cell and tissue damage by inhibiting aldose reduction and thereby reducing the accumulation intracellular sorbitol. Primary Mode of Action of Aldose Reductase Inhibitors: A major cause of diabetic neuropathy is the intraneural osmotic pressure that builds up as a consequence of the over-accumulation of sorbitol, a polyol formed by aldose reductase (Reaction: Glucose + NADPH ? Sorbitol + NADP+ + H+). Similar considerations apply to cataract formation in the lens, another tissue rich in aldose reductase. In diabetes, aldose reductase activity increases as the concentration of glucose rises in the lens, peripheral nerves and glomerulus (tissues that are insulininsensitive); because sorbitol lacks a membrane carrier, its contributes to intracellular osmotic pressure, disrupting cell-cell interactions (especially synapses), eventually leading to retinopathy and neuropathy. The additive effects of aldose reductase (AR) and polyol dehydrogenase in producing sorbitol from glucose and fructose, acting in combination with agedependent decreased hexokinase is believed to account for diabetic cataract formation in human lenses under high glucose stress. AR’s Km for glucose of AR is roughly 200 mM, whereas its Km for NADPH is 0.06 mM. NADP inhibits human lens AR noncompetitively and has a K1 that is roughly equal to the Km for NADPH. Notably. The Km for fructose is 40 mM and that for NADH is 0.02 mM in the polyol dehydrogenase (PD) reaction. Therefore, although sorbitol formation is modest during normoglycemia, such is not the case for diabetic hyperglycemia. Moreover, the recent increased reliance on high-fructose corn syrup as a sweetener is problematic, in that glucose-sensing mechanisms in humans are largely unresponsive to fructose. Because sorbitol is not transported out of the lens, any increase in intracellular sortbitol must be compensated osmotically by the considerable uptake of water, a well-characterized cataractogenic event. By inhibiting sorbitol dehydrogenase, alrestatin lowers tha undesirable net accumulatrion of sorbitol during hyperglycemic episodes. At high enough concentrations, alrestatin also inhibits PD. Target(s): aldose reductase, or aldehyde reductase; 4-aminobutyrate aminotransferase; carbonyl reductase; succinate-semialdehyde dehydrogenase; polyol dehydrogenase, weakly inhibited, except at elevated concentrations; hexonate dehydrogenase, or glucuronate reductase.
Check Digit Verification of cas no
The CAS Registry Mumber 51411-04-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,1,4,1 and 1 respectively; the second part has 2 digits, 0 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 51411-04:
(7*5)+(6*1)+(5*4)+(4*1)+(3*1)+(2*0)+(1*4)=72
72 % 10 = 2
So 51411-04-2 is a valid CAS Registry Number.
InChI:InChI=1/C14H9NO4/c16-11(17)7-15-13(18)9-5-1-3-8-4-2-6-10(12(8)9)14(15)19/h1-6H,7H2,(H,16,17)
51411-04-2Relevant articles and documents
Luminescent lanthanide-binding peptides: Sensitising the excited states of Eu(iii) and Tb(iii) with a 1,8-naphthalimide-based antenna
Bonnet, Celia S.,Devocelle, Marc,Gunnlaugsson, Thorfinnur
, p. 126 - 133 (2012)
The investigation into the luminescence properties of a lanthanide-binding peptide, derived from the Ca-binding loop of the parvalbumin, and modified by incorporating a 1,8-naphthalimide (Naph) chromophore at the N-terminus is described. Here, the Naph is used as a sensitising antenna, which can be excited at lower energy than classical aromatic amino acids, such as tryptophan (the dodecapeptide of which was also synthesised and studied herein). The syntheses of the Naph antenna, its solid phase incorporation into the dodecapeptide, and the NMR investigation into the formation of the corresponding lanthanide complexes in solution is presented. We also show that this Naph antenna can be successfully employed to sensitize the excited states of both europium and terbium ions, the results of which was used to determined the stability constants of their formation complexes, and we demonstrated that our peptide 'loop' can selectively bind these lanthanide ions over Ca(ii).
Exciton coupling in molecular salts of 2-(1,8-naphthalimido)ethanoic acid and cyclic amines: Modulation of the solid-state luminescence
D'Agostino, Simone,Grepioni, Fabrizia,Braga, Dario,Moreschi, Daniele,Fattori, Valeria,Delchiaro, Francesca,Di Motta, Simone,Negri, Fabrizia
, p. 10470 - 10480 (2013)
In this study we have purposely altered the solid state luminescence properties of 2-(1,8-naphthalimido)ethanoic acid (NEaH) (0) via molecular salts formation with cyclic amines such as 1,4-diazabicyclo[2.2.2]octane (DABCO), quinuclidine (ABCO), 3-quinuclidinol (OH-ABCO), and piperazine (PIP). All crystalline materials have been characterized in the solid state via single-crystal and variable temperature powder X-ray diffraction and thermal methods; luminescence spectra in the solid state have been recorded. Exciton interactions have been determined with quantum-chemical calculations for all molecular organic salts, and tuning of their magnitude in response to changes in the crystal packing has been demonstrated. It is suggested that the variations in photoluminescence can be interpreted on the basis of the different excitonic interactions amongst the naphthalimide moieties.
Variedly connected 1,8-naphthalimide-7-chloroquinoline conjugates: Synthesis, anti-mycobacterial and cytotoxic evaluation
Shalini,Johansen, Matt D.,Kremer, Laurent,Kumar, Vipan
, (2019)
Recent disclosures about anti-bacterial and anti-tubercular potential of naphthalimide and quinoline core respectively propelled us to synthesize a library of 1,8-naphthalimide-7-chloroquinoline hybrids. Different modes of linkage between two pharmacophoric units viz. simple alkyl chains and induction of amide bond were used and the substituents on the naphthalimide core were varied in order to determine Structure-Activity-Relationship (SAR). Our findings demonstrated that simple alkyl chain linked conjugates showed better activity profiles without any cytotoxicity, while the inclusion of amide bond enhanced the cytotoxic tendency. An interesting behaviour of conjugates in terms of activity and cytotoxicity was observed via switching over the nature of linker between two pharmacophores.
Closing the Loop: Triazolylpyridine Coordination Drives the Self-Assembly of Metallomacrocycles with Tunable Topologies for Small-Molecule and Guanine-Quadruplex Recognition
Miron, Caitlin E.,Colden Leung, Madelaine R.,Kennedy, Emily I.,Fleischel, Olivier,Khorasani, Mona Ashraf,Wu, Nan,Mergny, Jean-Louis,Petitjean, Anne
supporting information, p. 18718 - 18734 (2018/11/23)
The 2-(1,2,3-triazol-4-yl)pyridine motif, with its facile “click” synthesis and remarkable coordinative properties, is an attractive chelate for applications in the metal-directed self-assembly of intricate three-dimensional structures. Organic ligands th
