Hemi Synthesis, Anti-inflammatory and In-silico Alpha-amylase Inhibition of Novel Carlina Oxide Analogs

Numerous natural products have been successfully developed for clinical use in the treatment of human diseases in almost every therapeutic area.

This work aimed to synthesize some new analogs of carlina oxide by functionalizing the fifth position of the furan by different acyls groups using the Friedel-Crafts acylation approach, and then assess the in-vitro anti-inflammatory activity and in-silico alpha-amylase inhibition effect of carlina oxide and its synthetic analogs.

The new analogs were synthesized at room temperature using different anhydrides with the presence of boron trifluoride diethyl etherate (BF3Et2O) as acid catalyst. A protein denaturation assay was performed to evaluate the anti-inflammatory activity, while the molecular docking study was conducted using the Molecular Operating Environment (MOE) with three types of alpha-amylase sources: human salivary, pancreatic alpha-amylase and Aspergillus oryzae alpha-amylase (PDB: 1Q4N, 5EMY, 7P4W respectively).

A total of four analogs of carlina oxide were obtained in yields of 60-7% and then identified with ¹H and ¹³C NMR analysis. Additionally, analog 1 exhibited the better anti-inflammatory effect with IC50 of 0.280 mg/mL. However, the in-silico study showed that all the synthetic analogs have different interactions with human salivary alpha-amylase (1Q4N) and other interactions with 5EMY and 7P4W.

The new analogs of carlina oxide can have the potential to serve as an alternative agent for alpha-amylase inhibition, contributing to the reduction of postprandial hyperglycemia.