School Of Basic And Applied Sciences

Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/17

Browse

Has files: NoSubject: search.filters.subject.Diabetic complications

Search Results

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    Research progress on 2,4-thiazolidinedione and 2-thioxo-4-thiazolidinone analogues as aldose reductase inhibitors
    (Elsevier B.V., 2022-07-18T00:00:00) Kharyal, Ankush; Ranjan, Sanjeev; Jaswal, Shalini; Parveen, Darakhshan; Gupta, Ghanshyam Das; Thareja, Suresh; Verma, Sant Kumar
    Diabetes-associated complications are a major global health concern. In diabetics, the increased accumulation of sorbitol, produced via over activated polyol pathway, from glucose by the action of aldose reductase (AR, ALR2, or AKR1B1), has been associated with life-threatening co-morbidities. Aldose reductase is crucial in detoxifying certain hazardous aldehydes. However, aldose reductase overexpression in the hyperglycemic state results in microvascular and macrovascular diabetic complications through the consequences of the activated polyol pathway. Accordingly, aldose reductase inhibition has been identified as a viable strategy for dealing with diabetes-associated complications, and it has been put under investigation by various researchers around the world. 2,4-Thiazolidinedione (TZD) and its bio-isosteric analog 2-thioxo-4-thiazolidinone (rhodanine) have been explored as potential inhibitors of aldose reductase to find new molecules. The current review provides a comprehensive insight into the development and medicinal chemistry of TZD and rhodanine derivatives as aldose reductase inhibitors during the last twenty years (2002�2021). Here, the synthetic strategies, SAR, and binding mode of various compounds, Quantitative structure activity relationship (QSARs) are discussed with an emphasis on structural changes to the both moieties for optimizing/designing potent target-specific inhibitors, which is expected to be beneficial for the further design and discovery of newer agents for the treatment of diabetic complications. In addition, the patents on TZDs and rhodanine derivatives as aldose reductase inhibitors are summarized to illustrate the current status. � 2022 Elsevier B.V.
  • No Thumbnail Available
    Item
    Gaussian field-based comparative 3D QSAR modelling for the identification of favourable pharmacophoric features of chromene derivatives as selective inhibitors of ALR2 over ALR1
    (Springer, 2021-01-07T00:00:00) Verma, Sant Kumar; Kumar, Niraj; Thareja, Suresh
    Aldehyde reductase (ALR1) and aldose reductase (ALR2) are both oxo-reductase enzymes of aldo-keto reductase (AKR) superfamily involved in several cellular processes. ALR1 plays an important role in colorectal cancer, lungs, and hepatic carcinoma, while ALR2 is involved in diabetic complications like retinopathy, neuropathy, and nephropathy cataract. Both the enzymes take part in distinct physiological processes, however, share more > 70% structural homology. This is the major cause behind the unachieved target selectivity of molecules that entered the development pipeline as ALR2 inhibitors. Chromene analogues have been widely explored for diverse biological activities, including antioxidant and diabetic complication prevention potential. For the identification of spatial fingerprints of target-specific chromene bearing ALR2 inhibitors over ALR1, Gaussian field-based comparative 3D QSAR models were generated on a dataset having ALR1 and ALR2 inhibitory activity. Both the ALR1 and ALR2 3D QSAR models were statistically fit with good predictive ability concerning PLS generated validation constraints. The comparative steric, electrostatic, hydrophobic, HBA, and HBD features were elucidated using respective contour maps for selective target specific favourable activity against ALR2 over ALR1. In addition, the five-point pharmacophores for ALR1 and ALR2 favourable features were also generated using the DHHRR_1 hypothesis for better insight on the distinctive features of ALR2 inhibitors compared to ALR1. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
  • No Thumbnail Available
    Item
    Aldose Reductase: a cause and a potential target for the treatment of diabetic complications
    (Pharmaceutical Society of Korea, 2021-07-19T00:00:00) Thakur, Sapna; Gupta, Sonu Kumar; Ali, Villayat; Singh, Priyanka; Verma, Malkhey
    Diabetes mellitus, a disorder of metabolism, results in the elevation of glucose level in the blood. In this hyperglycaemic condition, aldose reductase overexpresses and leads to further complications of diabetes through the polyol pathway. Glucose metabolism-related disorders are the accumulation of sorbitol, overproduction of NADH and fructose, reduction in NAD+, and excessive NADPH usage, leading to diabetic pathogenesis and its complications such as�retinopathy, neuropathy, and nephropathy. Accumulation of sorbitol results in the alteration of osmotic pressure and leads to osmotic stress. The overproduction of NADH causes an increase in reactive oxygen species production which leads to oxidative stress. The overproduction of fructose causes cell death and non-alcoholic fatty liver disease. Apart from these disorders, many other complications have also been discussed in the literature. Therefore, the article overviews the aldose reductase as the causative agent and a potential target for the treatment of diabetic complications. So, aldose reductase inhibitors have gained much importance worldwide right now. Several inhibitors, like derivatives of carboxylic acid, spirohydantoin, phenolic derivatives, etc. could prevent diabetic complications are discussed in this article. � 2021, The Pharmaceutical Society of Korea.