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

2018; Elsevier BV; Volume: 274; Linguagem: Inglês

10.1016/j.molliq.2018.10.129

1873-3166

Francisco Xavier, C.T. Tavares, Marcelo Montenegro Rabello, Marcelo Zaldini Hernandes, Beatriz Pinheiro Bezerra, Alejandro P. Ayala, Otília Deusdênia Loiola Pessoa, Rafael Matos Ximenes, Nereide Stela Santos-Magalhães,

Drug Solubulity and Delivery Systems

The physicochemical stability and bioavailability of oncocalyxone A (onco A), a quinone isolated from Auxemma oncocalyx tree, could be improved by supramolecular 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-γ-CD inclusion complex, which was characterized by FTIR, 1HNMR, DSC and TG. Experimental results showed that onco A tends to interact more favorably with HP-γ-CD (K = 3175 M−1) with the most favorable Gibbs free energy (ΔG = −19.98 kJ.mol−1). Thermodynamic analysis indicates that the formation of the inclusion complex was entropy-driven (-TΔS = −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-γ-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-γ-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-γ-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.