Curcumin-Synthetic Analogs Library Screening by Docking and Quantitative Structure–Activity Relationship Studies for AXL Tyrosine Kinase Inhibition in Cancers
| Autor: | Loubna Allam, Lakhlili Wiame, Azeddine Ibrahimi, Fatima Ghrifi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Quantitative structure–activity relationship
Curcumin Binding pocket Quantitative Structure-Activity Relationship Antineoplastic Agents 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neoplasms Proto-Oncogene Proteins Genetics Humans Amino acid residue Protein Kinase Inhibitors Molecular Biology Research Articles 030304 developmental biology 0303 health sciences Kinase External validation Receptor Protein-Tyrosine Kinases Axl Receptor Tyrosine Kinase Molecular Docking Simulation Computational Mathematics Computational Theory and Mathematics Biochemistry chemistry Docking (molecular) 030220 oncology & carcinogenesis Modeling and Simulation Tyrosine kinase |
| Zdroj: | J Comput Biol |
| ISSN: | 1557-8666 |
| Popis: | AXL is an important drug target for cancers. Two-dimensional quantitative structure–activity relationship (2D-QSAR) tests were performed to elucidate a relationship between molecular structures and the activity of a series of 400 curcumin derivatives subjected to AXL kinase by ATP competition in the catalytic site. The partial least square regression method implanted in molecular operating environment software was applied to develop QSAR models, which were further validated for statistical significance by internal and external validation. The best model has proven to be statistically robust with a good predictive correlation of R(2) = 0.996 and a significant cross-validation correlation coefficient of q(2) = 0.707. Docking analysis reveled that three curcumin derivatives have the best affinity for AXL and formed a hydrogen bond with the important amino acid residues in the binding pocket. As treated in this article, the docking studies and 2D-QSAR approach will pave the way for the development of new drugs while highlighting curcumin and its derivatives. |
| Databáze: | OpenAIRE |
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