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
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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
