Abstract
α-Glucosidase, an enzyme involved in post-prandial hyperglycaemia, was used as a target to study the effect of compound(s) isolated from Goniothalamus wynaadensis and its isoxazoline derivatives. Among thirteen compounds screened, compounds 1, 3a and 3j exhibited significant inhibition with IC50 values of 63.42, 61.36 and 58.89 µg/mL, respectively, outperforming acarbose (71.72 µg/mL). Kinetic studies revealed competitive binding for compound 1 and uncompetitive/non-competitive binding for 3a and 3j. Fluorescence quenching showed a linear relationship between I0/I at different inhibitor concentrations. The binding sites in α-glucosidase were ≤ 1. The binding constants 3a (0.7307) > 3j (0.6563) > 1 (0.5415) displayed strong interactions. Docking study revealed binding affinities; 3j (–8.9) > 3a (–7.7) > 1 (–7), and acarbose, 1, 3a and 3j had ARG-312, PHE-157 interactions in common to α-glucosidase. The toxicity profile showed compounds fell in classes IV and V. Overall, the results indicate that compounds 1, 3a and 3j are effective against α-glucosidase.
Acknowledgement
The authors thank the University Grants Commission (UGC) and DST-Inspire for the financial assistance, and Central University of Karnataka – Department of Life Science and Chemistry for providing research facilities.
Author contributions
Kavya Sritha Bojja was involved in drafting of the manuscript, performed spectroscopic data, analysed and interpreted results. Akash Kumar performed experiments and analysed spectroscopic and biological data along with Kavya Sritha Bojja. Duraippandi Palanimuthu helped with fluorescence experiments and manuscript correction. Harish Holla worked in manuscript writing and correction. Kavishankar Gawli planned the research work, manuscript writing, correction, and coordination with all involved in the work and approved the final manuscript.
Disclosure statement
The authors report there are no competing interests to declare.
Data availability statement
All data produced or analysed in this study are included in the article.