Exploring the inclusion complex formation of 3-acetylcoumarin with β-cyclodextrin and its delivery to a carrier protein: A spectroscopic and computational study

Drug solubility is an important parameter to determine the biological efficacy of a drug. To avoid the difficulties of drug insolubility, macrocyclic hosts like cyclodextrins (CDs) are used to enhance the solubility through formation of inclusion complex. CDs are popular as drug-delivery vehicle as it dissociates the drug molecule at its binding destination, and has high biological tolerance. In this work, we report on the inclusion complex of 3-acetylcoumarin (3-AC) that induces apoptosis in breast cancer cells, with β-CD using steady-state and time-resolved fluorescence spectroscopy in tandem with molecular docking. We have further studied the transfer of 3-AC from β-CD inclusion complex to bovine serum albumin (BSA). Our spectroscopic and molecular docking results demonstrated that 3-AC forms a 1:2 inclusion complex with β-CD with high binding affinity. Moreover, the fluorescence resonance energy transfer and molecular docking results suggest that 3-AC partitions to the hydrophobic domain of BSA near the Trp 123. Our results demonstrate an efficient and convenient way of exploring bioavailability by increasing the aqueous solubility of biologically active 3-AC and its transfer to a carrier protein such as BSA.