keyword
MENU ▼
Read by QxMD icon Read
search

Aldose reductase inhibitor

keyword
https://www.readbyqxmd.com/read/27835059/epalrestat-an-aldose-reductase-inhibitor-prevents-glucose-induced-toxicity-in-human-retinal-pigment-epithelial-cells-in-vitro
#1
Srinivasan Senthilkumari, Rajendran Sharmila, Gowripriya Chidambaranathan, Ayyasamy Vanniarajan
PURPOSE: Aldose reductase (ALR), the first and rate-limiting enzyme involved in polyol pathway plays a central role in diabetes and its related complications, including diabetic retinopathy (DR). Inhibition of ALR may also be an ideal target for reducing the deleterious effects of DR. Therefore, the purpose of the present study was to investigate the protective effect of epalrestat (EPL), ALR inhibitor on glucose-induced toxicity in ARPE-19 cells. METHODS: ARPE-19 cells were challenged with normal glucose (NG, 5 mM) and high glucose (HG1, 25 mM and HG2, 50 mM) in the presence or absence of EPL...
November 11, 2016: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27769036/green-fluorescent-protein-chromophore-derivatives-as-a-new-class-of-aldose-reductase-inhibitors
#2
Ryota Saito, Maiko Hoshi, Akihiro Kato, Chikako Ishikawa, Toshiya Komatsu
A number of (Z)-4-arylmethylene-1H-imidazol-5(4H)-ones, which are related to the fluorescent chromophore of the Aequorea green fluorescent protein (GFP), have been synthesized and evaluated their in vitro inhibitory activity against recombinant human aldose reductase for the first time. The GFP chromophore model 1a, with a p-hydroxy group on the 4-benzylidene and a carboxymethyl group on the N1 position, exhibited strong bioactivity with an IC50 value of 0.36 μM. This efficacy is higher than that of sorbinil, a known highly potent aldose reductase inhibitor...
October 8, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27685794/in-vitro-and-in-vivo-inhibition-of-aldose-reductase-and-advanced-glycation-end-products-by-phloretin-epigallocatechin-3-gallate-and-6-gingerol
#3
Chethan Sampath, Shengmin Sang, Mohamed Ahmedna
Hyperglycemic stress activates polyol pathway and aldose reductase (AR) key enzyme responsible for generating secondary complications during diabetes. In this study the therapeutic potential of phloretin, epigallocatechin 3-gallate (EGCG) and [6]-gingerol were evaluated for anti-glycating and AR inhibitory activity in vitro and in vivo systems. Human retinal pigment epithelial (HRPE) cells were induced with high glucose supplemented with the phloretin, EGCG and [6]-gingerol. Aldose reductase activity, total advanced glycation end products (AGEs) and enzyme inhibitor kinetics were assessed...
September 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27666634/pterin-7-carboxamides-as-a-new-class-of-aldose-reductase-inhibitors
#4
Ryota Saito, Saori Suzuki, Kaname Sasaki
Aldose reductase is related to the onset and progression of diabetic complications, such as neuropathy, retinopathy, angiopathy, and so on: therefore molecules that are capable of inhibiting the enzyme are potential drugs for treatment of diabetic complications. Epalrestat is the sole aldose reductase inhibitor that is clinically used, but still has some drawbacks. Thus, the development of new aldose reductase inhibitors is still desired. We have synthesized a series of new pterin-7-carboxamides, and evaluated their in vitro inhibitory activities against human aldose reductase...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27639366/design-and-synthesis-of-chiral-2h-chromene-n-imidazolo-amino-acid-conjugates-as-aldose-reductase-inhibitors
#5
Gudipudi Gopinath, Venu Sankeshi, Shaym Perugu, Malini D Alaparthi, Srinivas Bandaru, Vijay K Pasala, Prasad Rao Chittineni, G L David Krupadanam, Someswar R Sagurthi
Aldose reductase (ALR2) inhibitors provide a viable mode to fight against diabetic complications. ALR2 exhibit plasticity in the active site vicinities and possible shifts in the nearby two supporting alpha helices. Therefore, a novel series of amino acid conjugates of chromene-3-imidazoles (13-15) were designed and synthesized based on natural isoflavonoids. The compounds were identified on the basis of spectral ((1)H NMR, (13)C NMR and MS) data and tested in vitro for ALR2 inhibitory activity with an IC50 value ranges from 0...
September 4, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27637378/construct-explicit-models-to-correlate-the-structure-and-the-inhibitory-activity-of-aldose-reductase-flavonoids-and-sulfonyl-pyridazinones-as-inhibitors
#6
Fengchao Cui, Lunyang Liu, Haifeng Tang, Kecheng Yang, Yunqi Li
The correlation between binding energies and bioactivities is the core of structure-based computer-aided drug design. However, many models to address this correlation are still strongly system-dependent at current stage. We constructed two explicit models to correlate the binding energies with the inhibitory activities of flavonoids and sulfonyl-pyridazinones as inhibitors of aldose reductase. The introduction of multiple complex states comprised of protein, coenzyme, substrate and inhibitor can remarkably improve the correlation coefficients, comparing with that using single complex state...
September 16, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27544072/coumarin-thiazole-and-oxadiazole-derivatives-synthesis-bioactivity-and-docking-studies-for-aldose-aldehyde-reductase-inhibitors
#7
Aliya Ibrar, Yildiz Tehseen, Imtiaz Khan, Abdul Hameed, Aamer Saeed, Norbert Furtmann, Jürgen Bajorath, Jamshed Iqbal
In continuation of our previous efforts directed towards the development of potent and selective inhibitors of aldose reductase (ALR2), and to control the diabetes mellitus (DM), a chronic metabolic disease, we synthesized novel coumarin-thiazole 6(a-o) and coumarin-oxadiazole 11(a-h) hybrids and screened for their inhibitory activity against aldose reductase (ALR2), for the selectivity against aldehyde reductase (ALR1). Compounds were also screened against ALR1. Among the newly designed compounds, 6c, 11d, and 11g were selective inhibitors of ALR2...
October 2016: Bioorganic Chemistry
https://www.readbyqxmd.com/read/27536992/sirt6-is-a-positive-regulator-of-aldose-reductase-expression-in-u937-and-hela-cells-under-osmotic-stress-in-vitro-and-in-silico-insights
#8
Ahmet Can Timucin, Huveyda Basaga
SIRT6 is a protein deacetylase, involved in various intracellular processes including suppression of glycolysis and DNA repair. Aldose Reductase (AR), first enzyme of polyol pathway, was proposed to be indirectly associated to these SIRT6 linked processes. Despite these associations, presence of SIRT6 based regulation of AR still remains ambiguous. Thus, regulation of AR expression by SIRT6 was investigated under hyperosmotic stress. A unique model of osmotic stress in U937 cells was used to demonstrate the presence of a potential link between SIRT6 and AR expression...
2016: PloS One
https://www.readbyqxmd.com/read/27396410/structure-activity-relationship-study-reveals-benzazepine-derivatives-of-luteolin-as-new-aldose-reductase-inhibitors-for-diabetic-cataract
#9
Jomon Sebastian
Hyperglycaemia in diabetic patients causes diverse range of complications and the earliest among them is diabetic cataract. The role of aldose reductase, the key enzyme in polyol pathway, is well known in the genesis of cataract in chronic diabetic patients. Controlling of sorbitol flux into lens epithelial cells through aldose reductase inhibitors is an important treatment strategy. Due to the side-effects of many drugs so far developed, the development of aldose reductase inhibitors from natural sources has gained considerable attention...
June 30, 2016: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/27359042/idd388-polyhalogenated-derivatives-as-probes-for-an-improved-structure-based-selectivity-of-akr1b10-inhibitors
#10
Alexandra Cousido-Siah, Francesc X Ruiz, Jindřich Fanfrlík, Joan Giménez-Dejoz, André Mitschler, Martin Kamlar, Jan Veselý, Haresh Ajani, Xavier Parés, Jaume Farrés, Pavel Hobza, Alberto D Podjarny
Human enzyme aldo-keto reductase family member 1B10 (AKR1B10) has evolved as a tumor marker and promising antineoplastic target. It shares high structural similarity with the diabetes target enzyme aldose reductase (AR). Starting from the potent AR inhibitor IDD388, we have synthesized a series of derivatives bearing the same halophenoxyacetic acid moiety with an increasing number of bromine (Br) atoms on its aryl moiety. Next, by means of IC50 measurements, X-ray crystallography, WaterMap analysis, and advanced binding free energy calculations with a quantum-mechanical (QM) approach, we have studied their structure-activity relationship (SAR) against both enzymes...
October 21, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27267001/a-series-of-pyrido-2-3-b-pyrazin-3-4h-one-derivatives-as-aldose-reductase-inhibitors-with-antioxidant-activity
#11
Zhongfei Han, Xin Hao, Bing Ma, Changjin Zhu
A series of pyrido[2,3-b]pyrazin-3(4H)-one based derivatives were designed as inhibitors of aldose reductase (ALR2), the enzyme which plays a key role in the development of diabetes complications as well as in the oxidative stress processes associated with diabetes and other pathologies. Most of the derivatives, having a substituted C2 aromatic group and a N4 acetic acid group on the core structure, were found to be potent and selective aldose reductase inhibitors with submicromolar IC50 values, and 9c was the most active with IC50 value 0...
October 4, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27233987/isolation-modification-and-aldose-reductase-inhibitory-activity-of-rosmarinic-acid-derivatives-from-the-roots-of-salvia-grandifolia
#12
Jie Kang, Yanbo Tang, Quan Liu, Nan Guo, Jian Zhang, Zhiyan Xiao, Ruoyun Chen, Zhufang Shen
To find aldose reductase inhibitors, two previously unreported compounds, grandifolias H and I, and five known compounds, including rosmarinic acid and rosmarinic acid derivatives, were isolated from the roots of Salvia grandifolia. A series of rosmarinic acid derivatives was obtained from rosmarinic acid using simple synthetic methods. The aldose reductase inhibitory activity of the isolated and synthesized compounds was assessed. Seven of the tested compounds showed moderate aldose reductase inhibition (IC50=0...
July 2016: Fitoterapia
https://www.readbyqxmd.com/read/27216445/active-site-fingerprinting-and-pharmacophore-screening-strategies-for-the-identification-of-dual-inhibitors-of-protein-kinase-c-formula-see-text-and-poly-adp-ribose-polymerase-1-parp-1
#13
Navriti Chadha, Om Silakari
Current clinical studies have revealed that diabetic complications are multifactorial disorders that target two or more pathways. The majority of drugs in clinical trial target aldose reductase and protein kinase C ([Formula: see text]), while recent studies disclosed a significant role played by poly (ADP-ribose) polymerase-1 (PARP-1). In light of this, the current study was aimed to identify novel dual inhibitors of [Formula: see text] and PARP-1 using a pharmaco-informatics methodology. Pharmacophore-based 3D QSAR models for these two targets were generated using HypoGen and used to screen three commercially available chemical databases to identify dual inhibitors of [Formula: see text] and PARP-1...
August 2016: Molecular Diversity
https://www.readbyqxmd.com/read/27208686/increased-sorbitol-levels-in-the-hypertrophic-ligamentumflavum-of-diabetic-patients-with-lumbar-spinal-canal-stenosis
#14
Jiaquan Luo, Lu Huang, Zhuo Chen, Zhaoxun Zeng, Takeshi Miyamoto, Hao Wu, Zhongzu Zhang, Zhimin Pan, Nobuyuki Fujita, Tomohiro Hikata, Akio Iwanami, Takashi Tsuji, Ken Ishii, Masaya Nakamura, Morio Matsumoto, Kota Watanabe, Kai Cao
The pathomechanism of the ligamentumflavum (LF) hypertrophy in diabetic patients with lumbar spinal canal stenosis (LSCS) remains unclear.A cross-sectional study was undertaken to investigate the mechanism of LF hypertrophy in thesepatients. Twenty-four diabetic and 20normoglycemic patients with LSCS were enrolled in the study. The structure of the LF in the study subjects was evaluated using histological and immunohistochemicalmethods, and thelevels of sorbitol, pro-inflammatory cytokines, and the fibrogenicfactor, TGF-β1,in the LF were analyzed...
May 21, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/27190083/ranirestat-has-a-stronger-inhibitory-activity-on-aldose-reductase-and-suppresses-inflammatory-reactions-in-high-glucose-exposed-endothelial-cells
#15
Yuji Ishibashi, Takanori Matsui, Takafumi Matsumoto, Hiroshi Kato, Sho-Ichi Yamagishi
OBJECTIVE: Under diabetic conditions, glucose is converted to sorbitol via aldose reductase, whose process could contribute to diabetic vascular complications. However, effects of aldose reductase inhibitors are modest in diabetic patients. This may be attributed to weak inhibitory activity of aldose reductase inhibitors. We compared effects of ranirestat on endothelial cell damage with those of epalrestat. MATERIALS AND METHODS: Intracellular formations of sorbitol and superoxide were measured by liquid chromatography-mass spectrometry-mass spectrometry and dihydroethidium staining, respectively...
July 2016: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/27189166/circulating-neutrophil-extracellular-trap-levels-in-well-controlled-type-2-diabetes-and-pathway-involved-in-their-formation-induced-by-high-dose-glucose
#16
Arina Miyoshi, Mai Yamada, Haruki Shida, Daigo Nakazawa, Yoshihiro Kusunoki, Akinobu Nakamura, Hideaki Miyoshi, Utano Tomaru, Tatsuya Atsumi, Akihiro Ishizu
OBJECTIVES: Although intensive therapy for type 2 diabetes (T2D) prevents microvascular complications, 10% of well-controlled T2D patients develop microangiopathy. Therefore, the identification of risk markers for microvascular complications in well-controlled T2D patients is important. Recent studies have demonstrated that high-dose glucose induces neutrophil extracellular trap (NET) formation, which can be a risk for microvascular disorders. Thus, we attempted to determine the correlation of circulating NET levels with clinical/laboratory parameters in well-controlled T2D patients and to reveal the mechanism of NET formation induced by high-dose glucose...
2016: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27156769/synthesis-of-benzothiadiazine-derivatives-exhibiting-dual-activity-as-aldose-reductase-inhibitors-and-antioxidant-agents
#17
Shaojuan Zhu, Xin Hao, Shuzhen Zhang, Xiangyu Qin, Xin Chen, Changjin Zhu
Several multifunctional benzothiadiazine derivatives were synthesized and examined for their inhibition to the enzyme aldose reductase and in vitro antioxidant activity to identify novel drugs for diabetes and its complications. Most of them exhibited good inhibitory activity. Importantly, a number of compounds demonstrated strong antioxidant activity and one compound in particular was extremely active in the DPPH radical scavenging and MDA inhibition analysis. The DPPH radical scavenging rate with this compound was 98...
June 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27153454/pyridothiadiazine-derivatives-as-aldose-reductase-inhibitors-having-antioxidant-activity
#18
Shaojuan Zhu, Shuzhen Zhang, Xin Hao, Xiangyu Qin, Shagufta Parveen, Shaoqi Yang, Bing Ma, Changjin Zhu
A series of aldose reductase (ALR2) inhibitors based on pyridothiadiazine were prepared and evaluated for their activities in ALR2 inhibition, DPPH scavenging, and MDA inhibition. Comparison studies were carried out between analogs having either hydroxyl or methoxy groups substituted on the N2-benzyl side chains of the compounds. Most of the hydroxy-substituted compounds were found to be more potent compared to their methoxy-substituted analogs with respect to DPPH inhibition (>93%) and MDA inhibition (>73%)...
May 6, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/27109517/bioactivity-focus-of-%C3%AE-cyano-4-hydroxycinnamic-acid-chca-leads-to-effective-multifunctional-aldose-reductase-inhibitors
#19
Laitao Zhang, Yi-Fang Li, Sheng Yuan, Shijie Zhang, Huanhuan Zheng, Jie Liu, Pinghua Sun, Yijun Gu, Hiroshi Kurihara, Rong-Rong He, Heru Chen
Bioactivity focus on α-cyano-4-hydroxycinnamic acid (CHCA) scaffold results in a small library of novel multifunctional aldose reductase (ALR2) inhibitors. All the entities displayed good to excellent inhibition with IC50 72-405 nM. (R,E)-N-(3-(2-acetamido-3-(benzyloxy)propanamido)propyl)-2-cyano-3-(4-hydroxy phenyl)acrylamide (5f) was confirmed as the most active inhibitor (IC50 72.7 ± 1.6 nM), and the best antioxidant. 5f bound to ALR2 with new mode without affecting the aldehyde reductase (ALR1) activity, implicating high selectivity to ALR2...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27102270/aldose-reductase-ocular-diabetic-complications-and-the-development-of-topical-kinostat-%C3%A2
#20
REVIEW
Peter F Kador, Milton Wyman, Peter J Oates
Diabetes mellitus (DM) is a major health problem with devastating effects on ocular health in both industrialized and developing countries. The control of hyperglycemia is critical to minimizing the impact of DM on ocular tissues because inadequate glycemic control leads to ocular tissue changes that range from a temporary blurring of vision to permanent vision loss. The biochemical mechanisms that promote the development of diabetic complications have been extensively studied. As a result, a number of prominent biochemical pathways have been identified...
September 2016: Progress in Retinal and Eye Research
keyword
keyword
75064
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"