Improvement of the solubility and anticancer activity of 6,8-dibromochrysin by encapsulation into β-cyclodextrin and its derivatives

Background

6,8-dibromochrysin (BrCN), a halogenated chrysin, possesses a profound bioactivity against dengue and Zika viruses and various types of cancer. However, the pharmaceutical applications of BrCN are limited by its poor aqueous solubility.

Methods

Molecular encapsulation of BrCN with beta-cyclodextrin (βCD) and its derivatives—2,6-di-O-methyl-beta-cyclodextrin (DMβCD) and 2-hydroxypropyl-beta-cyclodextrin (HPβCD)—was performed to enhance its water solubility, and the resulting inclusion complexes were characterized theoretically and experimentally.

Significant findings

Molecular docking showed that BrCN adopted two possible orientations, namely chromone ring insertion (C-form) and phenyl ring insertion (P-form) inside the lipophilic cavities of βCD, DMβCD, and HPβCD. Molecular dynamics (MD) simulations and the molecular mechanics with generalized Born and surface area solvation (MM-GBSA) method suggested that βCD derivatives show better BrCN-encapsulating potential as evidenced by their lower binding free energy values. Phase solubility study indicated a 1:1 stoichiometry between BrCN and the hosts (A_L type). The resulting inclusion complexes were characterized using scanning electron microscopy and differential scanning calorimetry. We noted that encapsulation with βCD, DMβCD, and HPβCD resulted in an approximately 27-fold, 92-fold and 104-fold increase in the aqueous solubility of BrCN, respectively and enhanced its anticancer activity against A549 and H1975 cancer cells.

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Khanittha Kerdpol, Amy Oo, Panupong Mahalapbutr, Duangjai Todsaporn, Siraphatsorn Phumphuang, Warinthorn Chavasiri, Thanyada Rungrotmongkol, Supot Hannongbua, Improvement of the solubility and anticancer activity of 6,8-dibromochrysin by encapsulation into β-cyclodextrin and its derivatives, Journal of the Taiwan Institute of Chemical Engineers, Volume 150, 2023, 105029, ISSN 1876-1070, https://doi.org/10.1016/j.jtice.2023.105029.

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