Synthesis and biological studies of novel fusidic acid-linked crown ethers

We successfully prepared novel Fusidic acid-linked crown ethers with various cavity sizes and fully characterised them using ¹H NMR,¹³C NMR (Broadband, DEPT-135, and DEPT-90), and ESI-MS. All the crown ethers and the precursor (Fusidic acid) were examined for their antioxidant and α-glucosidase inhibition activities. The crown ethers demonstrated excellent antioxidant activity, with IC₅₀ values ranging from 11.4 ± 0.54 to 45.6 ± 0.11 μM. They showed moderate α-glucosidase inhibitory effects, with IC₅₀ values ranging from 34.2 ± 0.23 to 65.7 ± 0.09 μM, compared to standards Butylated hydroxyanisole (IC₅₀ = 44.2 ± 0.36 μM) and deoxynojirimycin (IC₅₀ = 3.9 ± 0.71 μM), respectively. Notably, antioxidant activities increased in the crown ethers compared to parent Fusidic acid, highlighting the role of the crown moiety in enhancing activity. Molecular docking studies on human antioxidant proteins revealed that the most active antioxidant compounds exhibit fewer hydrogen bonds and higher alkyl bond interactions.