In silico design of new α-glucosidase inhibitors through 3D-QSAR study, molecular docking modeling and ADMET analysis
| Autor: | M. A. Ajana, A. Sbai |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| DOI: | 10.48317/imist.prsm/morjchem-v10i1.31722 |
| Popis: | α-Glucosidase enzyme is a therapeutic target for diabetes mellitus and its inhibitors shown a crucial importance in the treatment of this disease. Twenty oxindole based oxadiazole molecules were studied based on the combination between 3D-QSAR and molecular docking approaches in order to develop new α-glucosidase inhibitors with high predicted activities. The proposed CoMFA and CoMSIA models exhibited important Q2 values (0.544 and 0.605 respectively) and significant R2 values (0.977 and 0.935 respectively). The CoMFA and CoMSIA models were undergone to an external validation to test their proficiency; the produced R2test values are 0.950 and 0.804, respectively. Moreover, the contour maps produced by CoMFA and CoMSIA models have been exploited to determine the main groups influencing (decreasing or increasing) the α-glucosidase inhibitory activity. Therefore, two new oxindole based oxadiazole molecules with significant activities were proposed and designed. In a similar vein, molecular docking simulation was conducted to scrutinize the binding interactions between oxindole based oxadiazole molecules and α-glucosidase receptor (PDB code: 3A4A). Finally yet importantly, ADMET properties were predicted to assess the oral bioavailability of the proposed new compounds and examine their toxicity. Moroccan Journal of Chemistry, مجلد 10, عدد 1 (2022): in progress |
| Databáze: | OpenAIRE |
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