Browsing by Author "Gurvinder Singh"

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In Search of Novel SGLT2 Inhibitors by High-throughput Virtual Screening
(Bentham Science Publishers, 2024) Abhijit Debnath; Shalini Sharma; Rupa Mazumder; Avijit Mazumder; Rajesh Singh; Ankit Kumar; Arpita Dua; Priya Singhal; Arvind Kumar; Gurvinder Singh
Background: Type 2 diabetes mellitus constitutes approximately 90% of all reported forms of diabetes mellitus. Insulin resistance characterizes this manifestation of diabetes. The prevalence of this condition is commonly observed in patients aged 45 and above; however, there is an emerging pattern of younger cohorts receiving diagnoses primarily attributed to lifestyle-related variables, including obesity, sedentary behavior, and poor dietary choices. The enzyme SGLT2 exerts a negative regulatory effect on insulin signaling pathways, resulting in the development of insulin resistance and subsequent elevation of blood glucose levels. The maintenance of glucose homeostasis relies on the proper functioning of insulin signaling pathways, while disruptions in insulin signaling can contribute to the development of type 2 diabetes. Objective: Our study aimed to identify novel SGLT2 inhibitors by high-throughput virtual Screening. Methods: We screened the May bridge Hit Discover database to identify potent hits followed by druglikeness, synthetic accessibility, PAINS alert, toxicity estimation, ADME assessment, and consensus molecular docking. Results: The screening process led to the identification of three molecules that demonstrated significant binding affinity, favorable drug-like properties, effective ADME, and minimal toxicity. Conclusion: The identified molecules could manage T2DM effectively by inhibiting SGLT2, providing a promising avenue for future therapeutic strategies. © 2024 Bentham Science Publishers.
NMR based Serum metabolomics revealed metabolic signatures associated with oxidative stress and mitochondrial damage in brain stroke
(Springer, 2024) Sachin Yadav; Abhai Kumar; Smita Singh; Shahnawaz Ahmad; Gurvinder Singh; Abdul Rahman Khan; Rameshwar Nath Chaurasia; Dinesh Kumar
Brain stroke (BS, also known as a cerebrovascular accident), represents a serious global health crisis. It has been a leading cause of permanent disability and unfortunately, frequent fatalities due to lack of timely medical intervention. While progress has been made in prevention and management, the complexities and consequences of stroke continue to pose significant challenges, especially, its impact on patient’s quality of life and independence. During stroke, there is a substantial decrease in oxygen supply to the brain leading to alteration of cellular metabolic pathways, including those involved in mitochondrial-damage, leading to mitochondrial-dysfunction. The present proof-of-the-concept metabolomics study has been performed to gain insights into the metabolic pathways altered following a brain stroke and discover new potential targets for timely interventions to mitigate the effects of cellular and mitochondrial damage in BS. The serum metabolic profiles of 108 BS-patients were measured using 800 MHz NMR spectroscopy and compared with 60 age and sex matched normal control (NC) subjects. Compared to NC, the serum levels of glutamate, TCA-cycle intermediates (such as citrate, succinate, etc.), and membrane metabolites (betaine, choline, etc.) were found to be decreased BS patients, whereas those of methionine, mannose, mannitol, phenylalanine, urea, creatine and organic acids (such as 3-hydroxybutyrate and acetone) were found to be elevated in BS patients. These metabolic changes hinted towards hypoxia mediated mitochondrial dysfunction in BS-patients. Further, the area under receiver operating characteristic curve (ROC) values for five metabolic features (methionine, mannitol, phenylalanine, mannose and urea) found to be more than 0.9 suggesting their high sensitivity and specificity for differentiating BS from NC subjects. Graphical abstract: [Figure not available: see fulltext.] © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.