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

Author(s): Mohammed Auwal Ibrahim*, Murtala Bindawa Isah, Nasir Tajuddeen, Saadatu Auwal Hamza, Aminu Mohammed.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 7 , 2019

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Graphical 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.

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Article Details

Year: 2019
Page: [799 - 807]
Pages: 9
DOI: 10.2174/1570180815666180711110324
Price: $65

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