Preparation, characterization, and biological activity study of thymoquinone-cucurbit[7]uril inclusion complex

• Published in: RSC advances Vol. 12; no. 4; pp. 1982 - 1988
• Main Authors: Alrawashdeh, Lubna, Assaf, Khaleel I, Alshaer, Walhan, Odeh, Fadwa, Bani-Atta, Suhair A
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 12-01-2022; The Royal Society of Chemistry
• Subjects: Anticancer properties; Aqueous solutions; Binding; Biological activity; Chemistry; Complexation; Density functional theory; Drug carriers; Fluorescence; Inclusion complexes; Mathematical analysis; NMR spectroscopy; Spectrum analysis; Stoichiometry; Supramolecular compounds; Titration; Toxicity
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d1ra08460g

In this study, the formation of a host-guest inclusion complex between cucurbit[7]uril (CB[7]) and thymoquinone (TQ) was investigated in aqueous solution. The formation of a stable inclusion complex, CB[7]-TQ, was confirmed by using different techniques, such as
1
H NMR and UV-visible spectroscopy. The aqueous solubility of TQ was clearly enhanced upon the addition of CB[7], which provided an initial indication for supramolecular complexation. The complexation stoichiometry and the binding constant of the inclusion complex were determined through a combination of two sets of titration methods, including UV-visible and fluorescence displacement titrations. Both methods suggested the formation of a 1 : 1 stoichiometry between CB[7] and TQ with moderate binding affinity of 3 × 10
3
M
−1
. Density functional theory (DFT) calculations were also performed to verify the structure of the resulted host-guest complex and to support the complexation stoichiometry. The theoretical calculations were in agreement with experimental results obtained by
1
H NMR spectroscopy. Most importantly, the cytotoxic effect of the CB[7]-TQ complex was investigated against cancer and normal cell lines. The results showed that the anticancer activity of TQ against MDA-MB-231 cells was enhanced by the complexation with CB[7], while no significant effect was observed in MCF-7 cells. The results also confirmed the low toxicity of the CB[7] host molecule that supports the use of CB[7] as a drug carrier.
The host-guest inclusion complexation of thymoquinone by cucurbit[7]uril in aqueous solution is established, which results in an enhanced biological activity.