In silico and in vitro Evaluation of Microwave-Assisted Synthesized Isoxazole Chalcone Derivatives of Selected Phytoconstituents for Antidiabetic Activity

Background

Diabetes is a major chronic health problem worldwide that has acquired significant attention from the scientific community. One approach to managing glucose synthesis and reducing the risk of diabetes is through the inhibition of specific enzymes. Interestingly, heterocyclic compounds have been shown to effectively inhibit key enzymes involved in glucose metabolism, making them promising candidates for diabetes treatment.

Materials and Methods

In this study, we aimed to dock the α-glucosidase enzyme with 100 naturally derived inhibitors using PyRx software. Among these, 6 compounds were synthesized and evaluated for their pharmacological activity.

Results

In brief, from the initial screening, 50 compounds with a binding affinity greater than -7.2 kcal/mol were selected for further interaction analysis to aid in compound design. Notably, compounds SP2 and SP4-1-{3-nitro-5-[5-(quinolin-3yl)-4,5-dihydrofuran-3-yl]phenyl}ethan-1-one and (4-chlorophenyl){3-[5-(quinolin-3-yl)-4,5-dihydrofuran-3-yl]phenyl}methanone, respectively exhibited significantly higher α-amylase and α-glucosidase inhibitory activity showing 90.57% inhibition in the α-amylase assay and an 83.23% inhibition in the α-glucosidase assay to be comparable to acarbose, indicating strong therapeutic relevance.

Conclusion

Overall, the study demonstrated that the newly synthesized molecules possess medicinal potential against diabetes mellitus while adhering to Lipinski's rule of five.