Elucidation of the mechanism of complexation between oncocalyxone A and cyclodextrins by isothermal titration calorimetry and molecular modeling

The physicochemical stability and bioavailability of oncocalyxone A (onco A), a quinone isolated from Auxemma oncocalyx tree, could be improved by supramotecular inclusion complexes with cyclodextrins (CDs). The aim of this study was thus to elucidate the complexation of onco A with different CDs using isothermal titration calorimetry (ITC) and molecular modeling. Data from the most favorable host:guest interaction made it possible to obtain onco A:HP-gamma-CD inclusion complex, which was characterized by FTIR, (HNMR)-H-1, DSC and TG. Experimental results showed that onco A tends to interact more favorably with HP-gamma-CD (K = 3175 M-1) with the most favorable Gibbs free energy (Delta G = -19.98 kj-mol(-1)). Thermodynamic analysis indicates that the formation of the inclusion complex was entropy-driven (-T Delta S = -19.54 kj.mol(-1)), associated mainly with the hydrophobic interactions and release of water molecules from the cavity of the CD. Taken together, physicochemical analysis showed host:guest intermolecular interactions between onco A and the cavity of the HP-gamma-CD, thereby confirming the formation of the inclusion complex. Moreover, molecular docking results showed two main orientations in which the interaction of the hydroxyl group and a hydroxymethyl group at the wider rim of the HP-gamma-CD was more stable (average docking energy of -7.3 kcal/mol) than the one involving the methoxy group with two carbonyl groups at the wider rim (-7.1 kcal/mol). In conclusion, onco A:HP-gamma-CD inclusion complex based on results of rational approaches was obtained for use in for further pharmaceutical application in drug delivery systems in cancer therapy. Published by Elsevier B.V.