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Interaction of Stigmasterol with Trypanosomal Uridylyl Transferase, Farnesyl Diphosphate Synthase and Sterol 14α-demethylase: An In Silico Prediction of Mechanism of Action

[ Vol. 16 , Issue. 7 ]

Author(s):

Mohammed Auwal Ibrahim*, Murtala Bindawa Isah, Nasir Tajuddeen, Saadatu Auwal Hamza and Aminu Mohammed   Pages 799 - 807 ( 9 )

Abstract:


Background: Trypanosomiasis is one of the neglected tropical diseases and continues to cause serious morbidity, mortality and economic loss. Current anti-trypanosomal drugs are antiquated and suffer from a number of serious setbacks, thereby necessitating the search for new drugs. Stigmasterol has previously demonstrated in vitro and in vivo anti-trypanosomal activity.

Methods: Herein, stigmasterol was docked into three validated anti-trypanosomal drug targets; uridylyl transferase, farnesyl diphosphate synthase and sterol 14α-demethylase, in order to elucidate the possible biochemical targets for the observed anti-trypanosomal activity.

Results: The binding free energy between stigmasterol and the enzymes was in the order; sterol 14α-demethylase (-8.9 kcal/mol) < uridylyl transferase (-7.9 kcal/mol) < farnesyl diphosphate synthase (-5.7 kcal/mol). At the lowest energy docked pose, stigmasterol interacts with the active site of the three trypanosomal enzymes via non-covalent interactions (apart from hydrogen bond) while highly hydrophobic stigmasterol carbon atoms (21 and 27) were crucial in the interaction with varying residues of the three anti-trypanosomal targets.

Conclusion: Therefore, results from this study might suggest that stigmasterol mediated the antitrypanosomal activity through interaction with the three anti-trypanosomal targets but with more preference towards sterol 14α-demethylase.

Keywords:

Trypanosome, molecular docking, stigmasterol, uridylyl transferase, sterol 14α-demethylase, farnesyl diphosphate synthase.

Affiliation:

Department of Biochemistry, Ahmadu Bello University, Zaria, Department of Biochemistry, Umaru Musa Yar'adua University, Katsina, Department of Chemistry, Ahmadu Bello University, Zaria, Department of Chemistry, Ahmadu Bello University, Zaria, Department of Biochemistry, Ahmadu Bello University, Zaria

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