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

[ Vol. 14 , Issue. 2 ]

Author(s):

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

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.

Affiliation:

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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