COMPUTATIONAL PREDICTION OF SIDE EFFECTS OF ORAL ANTIDIABETIC DRUGS ON KIDNEY ENZYMATICS
DOI:
https://doi.org/10.55197/qjmhs.v5i2.192Keywords:
oral antidiabetics, side effects, molecular docking, binding affinityAbstract
Diabetes mellitus is a metabolic disorder that causes hyperglycemia and requires long-term treatment that carries the risk of side effects, including decreased kidney function. The study aims to determine the affinity and binding values between oral antidiabetic drugs and target proteins, as well as to computationally predict the toxicity and side effects of these drugs on renal enzymes using molecular docking and the Toxtree application. This study employs the molecular docking method to predict interactions and affinities between test compounds of oral antidiabetic drugs and target proteins. The affinity values of oral antidiabetic drugs toward ACE were as follows: Glimepiride -2.2 kcal/mol, Repaglinide 2.9 kcal/mol, Metformin -2.3 kcal/mol, Pioglitazone -2.0 kcal/mol, Acarbose 16.3 kcal/mol, Sitagliptin -1.9 kcal/mol, Dapagliflozin 0 kcal/mol, for the VDR protein: Glimepiride -11.2 kcal/mol, Repaglinide -8.1 kcal/mol, Metformin -5.1 kcal/mol, Pioglitazone -9.8 kcal/mol, Acarbose -7.6 kcal/mol, Sitagliptin -10.3 kcal/mol, Dapagliflozin -9.4 kcal/mol, on the EPOR protein: Glimepiride 16.0 kcal/mol, Repaglinide 0 kcal/mol, Metformin -3.3 kcal/mol, Pioglitazone -1.4 kcal/mol, Acarbose 14.2 kcal/mol, Sitagliptin -0.2 kcal/mol, Dapagliflozin -0.2 kcal/mol, on the COX-2 protein, namely Glimepiride -11.0 kcal/mol, Repaglinide -8.1 kcal/mol, Metformin -5.6 kcal/mol, Pioglitazone -9.1 kcal/mol, Acarbose -7.7 kcal/mol, Sitagliptin -9.7 kcal/mol, Dapagliflozin -8.5 kcal/mol. Based on computational analysis, Glimepiride and Sitagliptin exhibit the strongest and most stabel interactions, particularly with the VDR and COX-2 proteins, while Metformin and Dapagliflozin have lower affinities. Drug interactions with target proteins are dominated by hydrogen bonds, hydrophobic, and electrostatic interactions. It is predicted that oral antidiabetic drugs with side effects are Glimepiride and Sitagliptin.
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