Design of Novel Benzimidazole Derivatives as Potential α-amylase Inhibitors by 3D-QSAR Modeling and Molecular Docking Studies
| Autor: | Ayoub Khaldan, Khalil El Khatabi, Mohammed Bouachrine, M. A. Ajana, Reda El-Mernissi, Ilham Aanouz, Tahar Lakhlifi |
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| Rok vydání: | 2020 |
| Předmět: |
Quantitative structure–activity relationship
Benzimidazole Training set Molecular model molecular modeling Chemistry Multidisciplinary 3d-qsar computational study 3D-QSAR Molecular modeling Computational study Benzimidazole α-amylase inhibitors General Chemistry Computational biology benzimidazole lcsh:Chemistry chemistry.chemical_compound lcsh:QD1-999 chemistry α-amylase inhibitors Glycoside hydrolase Kimya Ortak Disiplinler Amylase inhibitors Antidiabetic agents |
| Zdroj: | Journal of the Turkish Chemical Society, Section A: Chemistry, Vol 7, Iss 2, Pp 471-480 (2020) Volume: 7, Issue: 2 471-480 Journal of the Turkish Chemical Society Section A: Chemistry |
| ISSN: | 2149-0120 |
| DOI: | 10.18596/jotcsa.703026 |
| Popis: | The α-amylase is an enzyme of a highly conserved glycoside hydrolase family, α-amylase inhibitors can be used as clinical agents for the treatment of Diabetes Mellitus (DM). A 3D-QSAR study was performed on 45 2-aryl benzimidazole derivatives, which have been identified as insulin-independent antidiabetic agents. The 3D-QSAR technique includes CoMFA with Q2 of 0.696 and R2 of 0.860 and CoMSIA with Q2 of 0.514 and R2 of 0.852. Both models were derived from a training set of 37 compounds based on an appropriate method of alignment, while the predictive ability was approved by a test set containing 8 compounds with rext2 values of 0.990 and 0.987, respectively. Moreover, contour maps generated from CoMFA and CoMSIA models provided much helpful information to figure out the features requirements that have control over the activity. To further reinforce the 3D-QSAR results, the molecular docking method was implemented which led to design new potent insulin-independent antidiabetic compounds with high predicted activity values. |
| Databáze: | OpenAIRE |
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