Host-Guest Complex of Cucurbituril with 5-Fluorouracil: Structural Study, Effect on Cytotoxicity, and Intracellular ROS Generation

Cucurbiturils are magnificent macrocycles that are used as precise molecules for the fabrication of supramolecular chemotherapeutic agents through host-guest molecular recognition. In the present work, the host-guest complex of cucurbit[6]uril (CB[6]) with 5-fluorouracil (Flu, an anticancer drug) is synthesized and its structural study was carried out using UV, XRD, and TG/DTA techniques. The UV-Vis spectrum of the inclusion complex exhibited maximum absorbance with a blue shift at 302 nm whereas the maximum absorbance for free CB[6] was observed at 318 nm. This notable shift in wavelength proves the formation of the inclusion complex of CB[6] with fluorouracil. The host-guest complex of fluorouracil with CB[6] shows sharp endothermic peaks at 403.30C with a heat flow of -0.5 mW/mg the peak covers partially an area of 528.2 J/g, The large variations observed in the DSC curves of the complex compared with free host CB[6] confirm the formation of a stable host-guest complex. The XRD pattern of the host-guest complex is different from the parent compound and this reaffirms the formation of host-guest complex. The cytotoxic effect of 5-fluorouracil and the host-guest complex of CB[6] with fluorouracil on KB cells was determined by MTT assay and the cytotoxicity of anticancer drug Flu towards cancer cells significantly increases by encapsulating 5-fluorouracil into the hydrophobic cavity of CB[6], The ROS generation study was carried out by measurement of intracellular ROS using fluorescent and chemiluminescent probe. The ROS generation of anticancer drugs against cancer cells is significantly increased by encapsulating 5-fluorouracil into the hydrophobic cavity of CB[6], The inclusion complex of cucurbituril with fluorouracil treatment in KB cells showed higher anticancer potential than fluorouracil treatment in KB cells when compared to the control. The IC 50 value of 5-flurouracil was found to be higher compared to the inclusion complex of cucurbituril with fluorouracil. The interesting results obtained, might open new avenues for the use of CB[6] host-guest complexes in anticancer and drug delivery studies.