In silico docking studies and in vitro xanthine oxidase inhibitory activity of commercially available terpenoids

Muthuswamy Umamaheswari,Puliyath Jagannath,Kuppusamy Asokkumar,Preetha Prabhu,Varadharajan Subhadradevi,Arumugam Madeswaran,Thirumalaisamy Sivashanmugam

doi:10.7439/ijpp.v2i5.617

Muthuswamy Umamaheswari, Puliyath Jagannath + Show 5 more

Open Access

https://doi.org/10.7439/ijpp.v2i5.617

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Abstract

Objective Xanthine oxidase is a highly versatile enzyme that is widely distributed among different species. The hydroxylation of purines is catalysed by xanthine oxidase and especially the conversion of xanthine to uric acid. Xanthine oxidase inhibitors are much useful, since they possess lesser side effects compared to uricosuric and anti-inflammatory agents. The present study deals with in silico and in vitro xanthine oxidase inhibitory analysis of commercially available terpenoids (bisabolol, β-caryophyllene, limonene, and α- terpinene). Methods Molecular docking studies were performed using AutoDock 4.2 and in vitro xanthine oxidase inhibitory activity was carried out using xanthine as the substrate. In addition, enzyme kinetics was performed using Lineweaver Burkplot analysis. Allopurinol, a known xanthine oxidase inhibitor was used as the standard. Results The results revealed that bisabolol exhibited a lowest binding energy value of about -7.33 kcal/mol. All other compounds showed binding energy values ranging between -7.33 to -5.87 kcal/mol which was less than the standard (-4.78 kcal/mol). In the xanthine oxidase assay, IC50 value of bisabolol was found to be 34.70

Highlights

Drug discovery is a linear process that begins with a target and lead, which is followed by lead optimization and in vitro and in vivo screening to determine if such compounds satisfy the preformulated criteria for initiating clinical development
It is based on Lamarckian Genetic Algorithm (LGA) which is a hybrid genetic algorithm with local optimization that uses a parameterized free-energy scoring function to estimate the binding energy[8]
We found a decrease in inhibition constant of all the selected terpenoids with a simultaneous decrease in the binding energy

Summary

Results

The results revealed that bisabolol exhibited a lowest binding energy value of about -7.33 kcal/mol. All other compounds showed binding energy values ranging between -7.33 to -5.87 kcal/mol which was less than the standard (-4.78 kcal/mol). In the xanthine oxidase assay, IC50 value of bisabolol was found to be 34.70 μg/ml, whereas that of allopurinol was 8.48 μg/ml. All the remaining compounds exhibited IC50 values ranging between 34.70 to 68.45 μg/ml. In the enzyme kinetic studies, bisabolol, β-caryophyllene showed non competitive and Limonene, α- terpinene and allopurinol showed competitive type of enzyme inhibition

Conclusion

Introduction

In silico docking studies