Molecular Docking Studies of Thiazolidinediones on Receptor for Advanced Glycation End Products (RAGE)
DOI:
https://doi.org/10.37285/ijpsn.2024.17.1.3Abstract
Background: Advanced glycation end products (AGE), are abnormal glycation of molecular proteins and nucleic acid, and its interaction with receptors for advanced glycation end products (RAGE) culminates in metabolic, neurodegenerative, and lifestyle disorders. Thiazolidinediones are insulin sensitizers with anti-glycation activity and are currently used clinically as anti-diabetic drugs.
Research rationale: Studies show that thiazolidinediones also exhibit antioxidant and antiglycation activity; hence we proposed that this anti-glycation activity of thiazolidinedione may be due to its anti-RAGE action, thus preventing further RAGE-AGE interaction.
Purpose of the study: Aim of the current study is to assess In-silico anti-RAGE activity of nine thiazolidinediones namely pioglitazone, rosiglitazone, ciglitazone, darglitazone, englitazone, netoglitazone, rivoglitazone, troglitazone and balaglitazone with RAGE.
Materials and Methods: Nine thiazolidinediones namely, pioglitazone, rosiglitazone, ciglitazone, darglitazone, englitazone, netoglitazone, rivoglitazone, troglitazone and balaglitazone were downloaded from PubChem database. RAGE protein was downloaded from the PDB database. The nine thiazolidinediones were docked with RAGE protein using Auto Dock software and interaction parameters were studied.
Result: All nine thiazolidinediones showed acceptable binding energy below (-8Kcal/mol) with 1-5 hydrogen bonds. Rosiglitazone exhibits the highest binding energy (-8.24Kcal/mol) with 2 hydrogen bonds for RAGE. Troglitazone exhibits the lowest binding energy (-9.95Kcal/mol) with 3 hydrogen bonds for RAGE.
Conclusion: Thus our Insilco docking studies of thiazolidinedione derivatives with RAGE conclude that these nine thiazolidinedione derivatives exhibit anti-glycation activity by direct interaction with receptors of RAGE. Thus, this work warrants future preclinical studies to claim its RAGE receptor modulation activity.
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Keywords:
RAGE, Thiazolidinediones, PPAR-response element, Adiponectin, AMPK
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