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Curcumin-Synthetic Analogs Library Screening by Docking and Quantitative Structure-Activity Relationship Studies for AXL Tyrosine Kinase Inhibition in Cancers.

Authors
  • Ghrifi, Fatima1
  • Allam, Loubna1
  • Wiame, Lakhlili1
  • Ibrahimi, Azeddine1
  • 1 The Biotechnology Lab (MedBiotech), BioInova Research center, Rabat Medical and Pharmacy School, Mohammed V University in Rabat, Rabat, Morocco. , (Morocco)
Type
Published Article
Journal
Journal of Computational Biology
Publisher
Mary Ann Liebert
Publication Date
Oct 01, 2019
Volume
26
Issue
10
Pages
1156–1167
Identifiers
DOI: 10.1089/cmb.2019.0052
PMID: 31009237
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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 R2 = 0.996 and a significant cross-validation correlation coefficient of q2 = 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.

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