Elucidation of the mechanism of complexation between oncocalyxone A and
cyclodextrins by isothermal titration calorimetry and molecular modeling
JOURNAL OF MOLECULAR LIQUIDS, (2019)DOI: 10.1016/j.molliq.2018.10.129
Abstract
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.