Identification of a New Isoindole-2-yl Scaffold as a Qo and Qi Dual Inhibitor of Cytochrome bc 1 Complex: Virtual Screening, Synthesis, and Biochemical Assay
| Autor: | Niusha Sharifi, Sophia Shahbazi, Kowsar Bagherzadeh, Massoud Amanlou, Homa Azizian |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Virtual screening Cytochrome biology Stereochemistry Assay Dual inhibitor Respiratory chain Health Informatics 010402 general chemistry environment and public health 01 natural sciences General Biochemistry Genetics and Molecular Biology 0104 chemical sciences Computer Science Applications enzymes and coenzymes (carbohydrates) 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry Oxidoreductase Coenzyme Q – cytochrome c reductase biology.protein Isoindole |
| Zdroj: | Interdisciplinary Sciences: Computational Life Sciences. 10:781-791 |
| ISSN: | 1867-1462 1913-2751 |
| DOI: | 10.1007/s12539-017-0241-8 |
| Popis: | Respiratory chain ubiquinol-cytochrome (cyt) c oxidoreductase (cyt bc 1 or complex III) has been demonstrated as a promising target for numerous antibiotics and fungicide applications. In this study, a virtual screening of NCI diversity database was carried out in order to find novel Qo/Qi cyt bc 1 complex inhibitors. Structure-based virtual screening and molecular docking methodology were employed to further screen compounds with inhibition activity against cyt bc 1 complex after extensive reliability validation protocol with cross-docking method and identification of the best score functions. Subsequently, the application of rational filtering procedure over the target database resulted in the elucidation of a novel class of cyt bc 1 complex potent inhibitors with comparable binding energies and biological activities to those of the standard inhibitor, antimycin. |
| Databáze: | OpenAIRE |
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