Hemisynthesis, Anti-Inflammatory, and In-silico Alpha-Amylase Inhibition of Novel Carlina Oxide Analogs

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Background: Numerous natural products have been successfully developed for clinical use in the treatment of human diseases in almost every therapeutic area. Objective: This work aimed to synthesize some new analogs of Carlina oxide by functionalizing the fifth position of the furan by different acyl groups using the Friedel-Crafts acylation approach. The synthetic analogs and carlina oxide were then assessed for their in-vitro anti-inflammatory activity and in-silico alpha-amylase inhibition effect. Methods: The new analogs were synthesized at room temperature using different anhydrides with the presence of boron trifluoride diethyl etherate (BF3-Et2O) as an acid catalyst. A protein denaturation assay was performed to evaluate the anti-inflammatory activity, while the in-silico study was conducted using the Molecular Operating Environment (MOE) with different types of alphaamylase sources, such as human salivary pancreatic alpha-amylase and Aspergillus oryzae alphaamylase (PDB: 1Q4N, 5EMY, 7P4W respectively). Results: 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 a better anti-inflammatory effect with an 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. Conclusion: The new analogs of Carlina oxide have the potential to serve as an alternative agent for alpha-amylase inhibition, contributing to the reduction of postprandial hyperglycemia.