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Current Computer-Aided Drug Design

Editor-in-Chief

ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

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 and Abidemi O. Olubiyi

Volume 14, Issue 2, 2018

Page: [106 - 116] Pages: 11

DOI: 10.2174/1573409914666180129163711

Price: $65

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.

Graphical Abstract

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