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

[ Vol. 14 , Issue. 2 ]


Olujide O. Olubiyi*, Maryam O. Olagunju, James O. Oni and Abidemi O. Olubiyi   Pages 106 - 116 ( 11 )


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.


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


Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Department of Biological Sciences, College of Science, Afe Babalola University, Ado-Ekiti, PMB 5454, Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, PMB 5454, State Specialist Hospital, Ikere-Ekiti

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