Psoralidin–cucurbit[7]uril complex with improved solubility to tackle human colorectal cancer: experimental and computational study

Nowdays, natural compounds are extensively studied for the prevention and treatment of various types of cancer due to their remarkable healing properties. In this field, encapsulating such natural anticancer agents into different delivery systems is a promising strategy for improving their therapeutic efficacy, selectivity, uptake into target tumor cells, and reducing adverse side effects. In this study, the supramolecular host–guest complexation of one of the promising bioactive compounds, Psoralidin (Ps), with cucurbit[7]uril (CB7) has been experimentally and computationally investigated. The Ps@CB7 complex has been characterized using 1H NMR and UV spectroscopy, phase solubility method, and DFT calculations. The phase solubility study suggests the 1 : 1 stoichiometry for the formed complexes and reveals the enhancement of the Ps solubility upon complexation. The stability constant of the host–guest complex has been computed to be 2.9 × 104 M−1, which corresponds to a complexation-free energy of −6.0 kcal mol−1. Morphology and dissolution studies have been performed. Ps, CB-7, and Ps@CB7 cytotoxicity was tested against colon cancer cells (HT-29). This was followed by apoptotic assay and cell cycle investigations for both the free drug (Ps) and the formulated complex (Ps@CB7). The obtained results clearly indicate that the guest molecule forms a stable complex with the CB7 host. Calculations show that non-covalent van der Waals interactions play the most decisive role in forming a stable adduct between the host and the guest. The formed Ps@CB7 exhibits a 9-fold enhanced cytotoxic activity against HT-29 colorectal cells compared to Ps. Apoptotic assay findings also revealed a remarkably higher percent cell population among the early apoptosis, late apoptosis, and necrosis quartiles in HT-29 cells treated with Ps@CB7 than their comparable, which were treated with Ps only (P-value ≤ 0.001). Ps@CB7 superseded the effects of Ps alone in arresting the cells at the G2 phase and reducing the number of cells undergoing DNA synthesis in the S phase (P-value ≤ 0.01). In conclusion, the novel Ps@CB7 complex would be an effective supramolecular system in the fight against cancer.