Structural Basis of Antisickling Effects of Selected FDA Approved Drugs: A Drug Repurposing Study

Author(s): Olujide O. Olubiyi*, Maryam O. Olagunju, James O. Oni, Abidemi O. Olubiyi.

Journal Name: Current Computer-Aided Drug Design

Volume 14 , Issue 2 , 2018

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Graphical Abstract:


Introduction: Sickle cell disease is characterized by a point mutation involving substitution of glutamic acid at position 6 to valine. Encoded in this hydrophobic mutation is both an intrinsic capacity for the beta globin molecules to assemble into thermodynamically favoured polymeric states as well as a rational way of interrupting the aggregation.

Methods: In this work, starting with a theoretical model that employs occlusive binding onto the beta globin aggregation surface and using a range of computational methods and an effective energy for screening, a number of FDA approved drugs with computed aggregation inhibitory activities were identified.

Results and Conclusion: The validity of the model was confirmed using sickling tests, after which pharmacophore models as well the structural basis for the observed antisickling effects were identified.

Keywords: Sickle cell, mutation, beta globin, pharmacophore models, antisickling, glutamic acid.

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Article Details

Year: 2018
Page: [106 - 116]
Pages: 11
DOI: 10.2174/1573409914666180129163711
Price: $58

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